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ABSTRACT: Critical interactions between the nervous system and the immune system during experimental autoimmune myasthenia gravis (EAMG) were examined in an animal model for human MG after immunization of adult female Lewis rats with Torpedo acetylcholine receptor (AChR) and complete Freund's adjuvant. Immunized rats depicted marked clinical severity of the disease. Using enzyme-linked immunospot (ELISPOT) assay and in situ hybridization techniques, immune responses in these animals were examined and showed elevated numbers of anti-AChR IgG secreting B cells and AChR reactive interferon (IFN)-gamma-secreting cells, enhanced mRNA expression of the proinflammatory cytokines IFN-gamma and tumour necrosis factor (TNF)-alpha as Th1 subset and the anti-inflammatory cytokines interleukin (IL)-4 and IL-10 as a Th2 subset, and transforming growth factor (TGF)-beta as a Th3 cytokine. Corticosterone and prostaglandin E(2) (PGE(2)) levels were measured by radioimmunoassay and illustrated increased production after immunization. Surgical denervation of the spleen reduced significantly the clinical severity of the disease, suppressed the numbers of IgG and IFN-gamma-secreting cells, down-regulated the mRNA expression for cytokines and reduced corticosterone and PGE(2) production. As controls, sham-operated rats were used and showed results as the EAMG non-denervated control rats. The data present herein, and for the first time, substantial effects of the nervous system on immune responses that may influence the outcome of EAMG. These effects were not dependent on cytokine inhibitory mediators such as prostaglandins or stress hormones. IL-10 and TGF-beta, the two potent immunosuppressive cytokines, were also suppressed, indicating a general suppression by splenic denervation. More investigations are initiated at our laboratories to understand the evident neural control over the immune system during challenges leading to the break of tolerance and development of autoimmunity, which may assist in innovative therapeutic approaches.
Clinical & Experimental Immunology 06/2006; 144(2):290-8. · 3.36 Impact Factor
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ABSTRACT: The aim of the present study was to investigate the effects of IL-1beta and Escherichia coli on the expression and secretion of MIP-2, the mouse equivalent to human IL-8, MCP-1 and RANTES in the kidneys of mice with acute pyelonephritis. Female Bki NMRI, as well as IL-1beta deficient mice and their wild-type littermates, were transurethrally infected with either E. coli CFT 073 or injected with NaCl 0.9% (w/v) and thereafter obstructed for 6 h. The Bki NMRI mice were killed at 0, 24, 48 h and 6 days and the IL-1beta-deficient mice at 48 h. Chemokine mRNA and protein levels peaked at 24 h for the tested chemokines with the mRNA expression localized in the tubular epithelial cells and for MIP-2 also in neutrophils. Obstruction per se, also induced a chemokine expression similar to E. coli infection although at a lower level. Interestingly, MIP-2 levels were higher in the IL-1beta deficient mice as compared with the wild-type littermates. Likewise, the inflammatory changes were more frequent and, when present, more widespread in the IL-1beta-deficient mice than in the wild-type mice. Stimulation of a human renal tubular epithelial cell line (HREC), A498 and of primary human mesangial cells (HMC) with the same bacterial antigen depicted gene expression of the same chemokines. A rapid release of IL-8 and MCP-1 was observed from both cell types. RANTES response was delayed both in the HREC and the HMC. We conclude that acute E. coli pyelonephritis induces a MIP-2/IL-8, MCP-1 and RANTES expression and secretion localized primarily to the epithelial cells and that this production is confirmed after in vitro stimulation with the same bacterial antigen of human epithelial and mesangial cells. Blockade of induction of chemokine response may thus be an attractive target for possible therapeutic intervention.
Clinical & Experimental Immunology 03/2003; 131(2):225-33. · 3.36 Impact Factor
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ABSTRACT: The most effective protection against human leishmaniasis has been achieved following vaccination with live promastigotes. Killed promastigotes + BCG can protect, albeit to a lower degree. To explore what mechanisms may be involved in these differences, the ability of live and dead promastigotes to induce immune responses were evaluated in vitro. The data showed that live and dead promastigotes differ in their ability to induce proliferation and cytokine production. Cytokine gene expression of Th1 related cytokines (IL-12, IFNgamma and TNFalpha) in adult PBMC was more evident to live than to heat killed promastigotes. This was coupled with significantly higher number of IFNgamma secreting cells induced by live than killed promastigotes. However, alpha-IL-12 antibodies did not block the IFNgamma response induced by live promastigotes. Proliferative responses were variable. In contrast to adult PBMC no IFNgamma secreting MNC could be detected in cord blood. However, in these cells the live promastigotes consistently induced higher proliferative response compared to dead. Implications of these findings are discussed.
Clinical & Experimental Immunology 05/2001; 124(1):43-53. · 3.36 Impact Factor
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ABSTRACT: Interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) are proinflammatory cytokines that are thought to play a role in bone remodeling, bone resorption, and new bone deposition. In the present work, in situ hybridization was performed to measure the messenger RNA expression of IL-1beta, IL-6, and TNF-alpha at 3, 7, and 10 days after the application of orthodontic force on the maxillary first molars of 12 rats. The contralateral side and 3 untreated rats served as controls. Measurements of the messenger RNA expression were selected as the means to investigate the role of orthodontic force in de novo synthesis of proinflammatory cytokines. After the application of force, the induction of IL-1beta and IL-6 was observed to reach a maximum on day 3 and to decline thereafter. No messenger RNA induction of either cytokine was measured in the control teeth. The messenger RNA expression of TNF-alpha was not detected at any time point of this study in the experimental or contralateral sides or in the control animals. Our data support the hypothesis that these proinflammatory cytokines may play important roles in bone resorption after the application of orthodontic force.
American Journal of Orthodontics and Dentofacial Orthopedics 04/2001; 119(3):307-12. · 1.38 Impact Factor
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ABSTRACT: Chemokines are small-secreted proteins that stimulate the directional migration of leukocytes and thereby mediate the inflammatory process. The present study investigates the capacity of human gingival fibroblasts to produce the beta chemokine Rantes/CCL5. In situ hybridization, immunohistochemistry and ELISA were used to measure the induction of Rantes/CCL5 at the mRNA and protein levels, both in unstimulated gingival fibroblasts as well as in fibroblasts treated with the proinflammatory cytokines tumor necrosis factor (TNF)alpha or interleukin (IL)-1beta. TNFalpha in different concentrations (0.1-10 ng/ml) induced Rantes/CCL5 mRNA expression and protein production in 24-h cultures of human gingival fibroblasts. The expression of Rantes/CCL5-mRNA and protein production, induced by TNFalpha, was evident at 6 h and thereafter increased continuously during the study period (24 h). IL-1beta (3-300 pg/ml) also enhanced the production of Rantes/CCL5 in gingival fibroblasts. The amount of Rantes/CCL5 induced by IL-1beta (300 pg/ml), however, was less than that induced by TNFalpha (10 ng/ml). The study suggests that human gingival fibroblasts, by producing the chemokine Rantes/CCL5, participate in the regulation of the host response during the inflammatory process in the periodontal tissue.
European Journal Of Oral Sciences 03/2001; 109(1):44-9. · 1.88 Impact Factor
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ABSTRACT: We have examined the role of alpha and beta chemokines in the promotion of the ontogenetic development of the brain. RANTES was expressed preferentially in human fetal astrocytes in an age-dependent manner. Astrocytes from 5-week-old brains showed high proliferation and reduced survival, whereas 10-week-old astrocytes exhibited opposite effects. These effects were suppressed by anti-RANTES or anti-RANTES receptor antibodies and were enhanced by recombinant RANTES. RANTES induced tyrosine phosphorylation of several cellular proteins and nuclear translocation of STAT-1 in astrocytes. Interferon-gamma (IFN-gamma) was required for RANTES effects because RANTES induced IFN-gamma and only 10-week-old astrocytes expressed the IFN-gamma receptor. Blocking of IFN-gamma with antibody reversed the effects of RANTES, indicating that cytokine/chemokine networks are critically involved in brain development.
Nature Cell Biology 03/2001; 3(2):150-7. · 19.49 Impact Factor
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ABSTRACT: The aim of this study was to investigate the influence of IL-6 on mortality, bacterial growth and cytokine expression in experimental acute pyelonephritis. Female IL-6-deficient mice and their wild-type counterparts, 8-10 weeks old, were infected with Escherichia coli CFT 073 or injected with NaCl 0.9% (w/v) via the urethra and thereafter obstructed for 6 h. Animals were killed at 48 h, 6 days or 8 weeks and cytokine and bacterial renal levels were assessed at each time point. We found that IL-6-deficient mice had increased mortality and extensive renal bacterial growth on day 6, compared with wild-type mice (P < 0.05) and the histopathological changes were generally more severe and widespread in the IL-6-deficient mice. Peak mRNA expression of IL-1beta, IL-4, IL-10, IL-12 and interferon-gamma (IFN-gamma) occurred 48 h after infection in both IL-6 knock out and wild-type mice. Transforming growth factor-beta (TGF-beta) levels also peaked at 48 h in E. coli-infected wild-type mice, while in the IL-6-deficient strain both TGF-beta mRNA and protein levels were significantly lower at 48 h than wild-type levels (P < 0.0008 and P < 0.03, respectively) and remained stationary throughout the study period. Animals injected with NaCl 0.9% (w/v) displayed a similar decrease in TGF-beta expression (P < 0.02). When splenocytes from the IL-6-deficient mice were incubated with murine recombinant IL-6, TGF-beta levels increased to those of wild-type mice. No increase was observed when splenocytes from wild-type mice were incubated with the same doses of rIL-6. We therefore conclude that IL-6 plays an important role in bacterial clearance and directly influences the TGF-beta levels in experimental acute pyelonephritis. We also demonstrate that urethral obstruction per se induces an increase in TGF-beta the magnitude of which is decreased in IL-6-deficient mice.
Clinical & Experimental Immunology 12/2000; 122(2):200-6. · 3.36 Impact Factor
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ABSTRACT: The effect of triclosan (2,4,4'-trichloro-2'-hydroxyl-diphenyl ether) on the production of interferon-gamma (IFN-gamma) and the expression of major histocompatibility complex (MHC) class II antigen was studied in human gingival fibroblasts isolated from 4 individuals.
All cell lines demonstrated high IFN-gamma production in 24-h cultures of human gingival fibroblasts stimulated by phytohemagglutinin (PHA) (5 microg/ml). Human gingival fibroblasts showed a high expression of MHC class II when stimulated with 500 and 1,000 pg/ml rIFN-gamma in 7-day cultures. Treatment of the cells with triclosan (0.5 microg/ml) reduced both IFN-gamma production and MHC class II expression in human gingival fibroblast cultures. Similar inhibitory effects on IFN-gamma production and MHC class II expression were observed when the anti-inflammatory agent dexamethazone (1 microM) was used.
The present study further supports the view that the agent has an anti-inflammatory effect in addition to its antibacterial capacity.
Journal Of Clinical Periodontology 11/2000; 27(10):733-7. · 3.00 Impact Factor
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ABSTRACT: To study the effect of an angiotensin II type 1 receptor antagonist, losartan, on cytokine expression, kidney growth and renal scarring in experimental acute pyelonephritis.
Female Bki NMRI mice, 8 weeks old were infected with E. coli CFT 073 via the urethra. Mice were divided into four groups; either left untreated; or treated with NaCl 0.9%; or an angiotensin II type 1 receptor antagonist, losartan, in doses of 1 mg. or 40 mg. /kg. body weight. The treatment was given daily i.p. for 48 hours, 3 weeks or 8 weeks respectively. Kidneys were weighed and sectioned for histo-pathology and in situ hybridization for mRNA of IL-1beta, TNF-alpha, IL-4, IL-6, IL-10, IL-12, TGF-beta and IFN-gamma. Homogenized kidneys were used for EIA of TGF-beta and bacterial growth.
The mRNA expression of the studied cytokines generally peaked at 48 hours in all four groups. In animals treated with losartan, kidney TGF-beta, IFN-gamma and IL-6 decreased significantly at 3 and 8 weeks as compared with controls, untreated or those treated with NaCl, (p <0.005 respectively). Infection was associated with a declining kidney weight, also in the presence of losartan. A 50% reduction of the spread of renal scarring was observed in the losartan treated group, but this did however not reach significance. The proportion of kidneys showing bacterial growth was not influenced by losartan although in these kidneys the mean bacterial counts at 3 weeks were significantly higher in the losartan treated mice (p <0.006).
Losartan is associated with downregulation of TGF-beta, IFN-gamma and IL-6 and may, in combination with antimicrobial therapy, reduce the risk of cortical renal scarring in recurrent acute pyelonephritis in infants.
The Journal of Urology 08/2000; 164(1):186-91. · 3.75 Impact Factor
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ABSTRACT: Interferon gamma (IFN-gamma) is a potential immunoregulatory cytokine, which is secreted mainly by cells of immune origin. In this study, we examined the capacity of human gingival fibroblasts as non-professional immune cells to express IFN-gamma messenger RNA (mRNA) and to produce the protein. Cultures of fibroblast cells were established from gingival biopsies from three children. The expression of mRNA for IFN-gamma was studied by in situ hybridization, and the level of IFN-gamma was determined by cell-released capturing ELISA. Treatment of the cells with phytohaemagglutinin (PHA) (2.5, 5.0, and 10 microg/ml) increased the number of IFN-gamma mRNA expressing cells and the protein production at 1, 6, and 24 h. Non-stimulated cells did not reveal measurable levels of IFN-gamma mRNA or the protein. The inflammatory cytokines interleukin 1beta (IL-1beta) (100 microg/ml) and tumour necrosis factor alpha (TNFalpha) (10 ng/ml) did not affect IFN-gamma mRNA expression or protein production. Treatment of the cells with 1 microM phorbol 12-myristate-13-acetate (PMA) stimulated IFN-gamma mRNA expression but had no effect on IFN-gamma protein production. We conclude that human gingival fibroblasts not only transcribe IFN-gamma mRNA but also produce the IFN-gamma protein in response to PHA. The finding that human gingival fibroblasts, produce the cytokine IFN-gamma, further support the concept that these cells take an active part in the modulation of the inflammatory and immune response in the periodontal tissue.
Cytokine 05/2000; 12(4):368-73. · 3.02 Impact Factor
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ABSTRACT: Bidirectional signalling between Trypanosoma brucei brucei and CD8+ T cells involves reciprocal action of the parasite-derived trypanosome derived lymphocyte triggering factor (TLTF) and lymphocyte-derived IFN-gamma. Herein we further characterize this relationship and report quantitation of TLTF secretion into culture supernatants using a newly developed ELISA. Secretion is induced by IFN-gamma in a dose-response manner, with 100 U/ml giving maximal yields of bioactive TLTF as assessed by ELISA and ELISPOT. This is a constitutive and active secretion. Furthermore, IFN-gamma-induced secretion was dependent on tyrosine protein kinase activity. Specific blockers of this signalling system resulted in lower yields of TLTF in the culture supernatants.
Parasitology 04/2000; 120 ( Pt 3):281-7. · 2.96 Impact Factor
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ABSTRACT: African trypanosomiasis is characterized by progressive central nervous system (CNS) involvement. Using single and double immunohistochemistry, we evaluated the induction of alpha- and beta-chemokines in brains of Sprague-Dawley rats infected with Trypanosoma brucei brucei (T. b. brucei) and identified their cellular source. The results showed high production of MIP-2, RANTES and MIP-1alpha and to a lower extend MCP-1 in infected animals compared to controls. MIP-2, RANTES and MIP-1alpha were produced early by astrocytes and microglia and later by macrophages and T-cells. These findings suggest that chemokines may contribute to the immunopathogenesis that occurs in the CNS early during infections.
Journal of Neuroimmunology 04/2000; 103(2):165-70. · 2.96 Impact Factor
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ABSTRACT: Bidirectional signalling between Trypanosoma
brucei
brucei and CD8+
T cells involves reciprocal action of the parasite-derived trypanosome derived lymphocyte triggering factor (TLTF) and lymphocyte-derived IFN-γ. Herein we further
characterize this relationship and report quantitation of TLTF secretion into culture supernatants using a newly developed
ELISA. Secretion is induced by IFN-γ in a dose–response manner, with 100 U/ml giving maximal yields of bioactive
TLTF as assessed by ELISA and ELISPOT. This is a constitutive and active secretion. Furthermore, IFN-γ-induced
secretion was dependent on tyrosine protein kinase activity. Specific blockers of this signalling system resulted in lower
yields of TLTF in the culture supernatants.
Parasitology 02/2000; 120(03):281 - 287. · 2.96 Impact Factor
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ABSTRACT: To examine critical interactions between the nervous system and the immune system during experimental African trypanosomiasis.
Inoculation of Trypanosoma brucei brucei resulted in early interferon (IFN)-gamma production, elevated corticosterone and prostaglandin E(2) (PGE(2)) levels and increased splenocyte proliferation, as measured by enzyme-linked immunospot assay, radioimmunoassay and thymidine incorporation assay, respectively. Splenic denervation suppressed IFN-gamma, corticosterone and PGE(2) production, enhanced splenocyte proliferation, and significantly reduced parasitemia and prolonged rat survival.
Our data show substantial effects of the nervous system on early immune responses that may influence the outcome of this disease. These effects were not dependent on cytokine inhibitory mediators such as prostaglandins or stress hormones. More investigations are required to understand the evident neural control over the immune system during infectious challenges, which may assist in novel therapeutic approaches.
NeuroImmunoModulation 02/2000; 8(1):31-8. · 2.38 Impact Factor
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ABSTRACT: Cytokines are important signaling proteins that are liberated during immune challenges and exhibit many modulatory activities. However, their role in periodontal modeling during orthodontic tooth movement is not fully understood. The aim of this study was to analyze effects of mechanical force during orthodontic tooth movement, in the pressure zone, on the induction of interferon-gamma (IFN-gamma) as a proinflammatory cytokine of Th1 type and interleukin-4 (IL-4)/IL-10 as anti-inflammatory cytokines of Th2 type. In 12 Wistar rats 40-45 days old, the maxillary first molar was moved mesially by means of a closed coil spring for 3, 7, and 10 days. The contralateral side served as a control. IFN-gamma, IL-4, and IL-10 mRNA were determined by in situ, hybridization, and protein levels of IFN-gamma was measured by immunohistochemistry. Induction of IFN-gamma at both mRNA and protein levels was significantly higher on the experimental side than on the contralateral control side on day 3. The signal gradually became stronger on day 7 and remained high on day 10. Cytokines of the Th2 type (IL-4 and IL-10) were not detected at all examined time points in both pressure and contralateral control sides. Considering the potential immunoregulatory roles played by IFN-gamma, our data suggest that IFN-gamma may be involved in periodontium remodeling during orthodontic tooth movement.
Journal of Interferon & Cytokine Research 02/2000; 20(1):7-12. · 3.06 Impact Factor
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ABSTRACT: Dorsal root ganglia (DRG) were shown to express neuronal interferon (IFN)-gamma, which supports Trypanosoma brucei brucei growth. The ability of a trypanosome-derived factor (TLTF) to activate DRG to neuronal IFN-gamma secretion was investigated, together with the signaling pathway that might be involved during this process. Immunohistochemical staining revealed expression of neuronal IFN-gamma on stimulation with TLTF, which was blocked with the tyrosine protein-kinase inhibitor, tyrphostin A47. Western blot was used to analyze DRG lysates prepared at different time points after stimulation with TLTF. A tyrosine-phosphorylated protein induced at 15 min was seen as a band of 120-150 kDa, followed by a decrease to control levels after 30 min. A47 greatly suppressed the TLTF-induced tyrosine protein kinase activity. In addition, evidence suggesting that the transcription factor STAT-1 may play a key role in the TLTF signaling pathway was provided by the blocking effects of A47 on STAT-1 translocation to the nucleus.
The Journal of Infectious Diseases 01/2000; 181(1):400-4. · 6.41 Impact Factor
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ABSTRACT: The cross talk between the central nervous system (CNS) and the immune system includes among others, the modulation of immune responses by the autonomic nervous system. Here, we investigated the effects of a splenic denervation on cytokine induction in early experimental African trypanosomiasis. Profiles of the cytokine mRNA expression for interleukin (IL)-4, interleukin (IL)-6, interleukin (IL)-10, interleukin (IL)-12, tumour necrosis factor (TNF)-alpha, tumour necrosis factor (TNF)-beta, transforming growth factor (TGF)-beta and interferon (IFN)-gamma were examined at 4 h, 8 h and 12 h postinfection (p.i.), and in noninfected controls. Only IFN-gamma and IL-12 were significantly expressed over noninfected controls. Already at 4 h p.i. both cytokines were expressed and showed more increased levels at 12 h. Sympathetic denervation of the spleen markedly reduced the mRNA expression for both IFN-gamma and IL-12. Con A was used as a positive control and showed an enhanced mRNA expression, which was also suppressed by a splenic denervation. To demonstrate that the mRNA expression had resulted in a cytokine production, we looked for the protein level of IFN-gamma at 4 h p.i. by immunohistochemistry and found increased levels of IFN-gamma, which was also inhibited by the denervation. Sham-operated animals exhibited similar responses as the nondenervated controls. Our data present for the first time very early kinetics for a cytokine gene expression during an experimental African trypanosomiasis. Furthermore, the data suggest a regulatory role for the autonomic nervous system on cytokine responses at both the mRNA and the protein levels.
Scandinavian Journal of Immunology 12/1999; 50(5):485-91. · 2.23 Impact Factor
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ABSTRACT: In the early stage of orthodontic tooth movement, an acute inflammatory response characterized by the migration of leukocytes occurs. This response suggests the presence of specific chemotactic signals that may play a role in the mechanism of bone remodeling, in particular in resorption. The aim of the present study was to explore the induction of potential chemokines at the resorption side during orthodontic tooth movement. Monocyte chemoattractant protein-1 (MCP-1), regulated on activation normal T cell expressed and secreted (RANTES), and macrophage inflammatory protein-2 (MIP-2) were examined by in situ hybridization using radioactive synthetic oligoneucleotide probes. Mesial movement of the upper first molars was performed with a fixed appliance for 3, 7, and 10 days. The results demonstrated that MCP-1, RANTES, and MIP-2 were highly expressed during orthodontic movement. On day 3, MCP-1 showed maximum induction in the pressure zone, followed in intensity by RANTES and MIP-2, although not in the contralateral control side. The induction of these chemokines had declined on day 7 and reached low levels on day 10. Our data suggest that chemokines are induced early in the application of force, and such induction may contribute to the early inflammatory response that may be responsible in part for the ensuing bone remodeling.
Journal of Interferon & Cytokine Research 10/1999; 19(9):1047-52. · 3.06 Impact Factor
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ABSTRACT: Cytokines are important signalling proteins, which have been shown to contribute to immunopathogenesis of several inflammatory and infectious diseases such as African trypanosomiasis. The present study was conducted in order to evaluate the early induction of five potential cytokines in the central nervous system (CNS) and spleens from Trypanosoma brucei brucei (T. b. brucei)-inoculated and uninfected control Sprague-Dawley rats. In brain, choroid plexus and spleen, cytokine levels were examined by in situ hybridization and immunohistochemistry, while ELISA was used to measure cytokine levels in cerebrospinal fluid (CSF). Our results showed that interferon (IFN)-gamma and transforming growth factor (TGF)-beta were highly expressed in all compartments, but low interleukin (IL)-4, IL-10 and tumour necrosis factor (TNF)-alpha mRNA levels were registered. The pattern of these cytokines is in context with the severity of the disease because (i) IFN-gamma was previously demonstrated to promote parasite growth (ii) TNF-alpha was previously demonstrated to kill the parasites and (iii) IL-4 was previously demonstrated to promote antibody production necessary for elimination of the infection. These data support the hypothesis that cytokines may have a role in developing the disease either by enhancing the parasite growth or by suppressing the immune response.
Scandinavian Journal of Immunology 10/1999; 50(3):256-61. · 2.23 Impact Factor
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ABSTRACT: To study the involvement of cytokines and their corresponding autoantibodies (Aabs) in inflammatory mechanisms in patients with lower respiratory tract infections, blood samples were taken from patients at the time of admission to the hospital and before treatment. Cell-released capturing enzyme-linked immunosorbent assay was used to measure the levels of gamma interferon (IFN-gamma) and interleukin-4 (IL-4) produced spontaneously by peripheral mononuclear cells (PMNC). ELISA was used to measure Aabs to these cytokines in sera. The levels of both cytokines were inversely related to the levels of their corresponding Aabs. While a high level of IFN-gamma was observed together with a low level of anti-IFN-gamma Aab, decreased IL-4 levels were observed with increased levels of Aabs to IL-4. Immunoglobulins were purified, digested to obtain Fab fragments, and tested for specificity and cross-reactivity. The Aabs and their Fab fragments were tested in cytokine biological assays and showed neutralizing effects. Our data demonstrated increased levels of the proinflammatory cytokine IFN-gamma and decreased release of the anti-inflammatory cytokine IL-4 during early presentation of lower respiratory tract infection. The levels of these cytokines were inversely related to the levels of their corresponding Aabs that exhibited regulatory effects on the cytokine biological function in vitro.
Infection and Immunity 07/1999; 67(6):3051-4. · 4.16 Impact Factor
