Effect of chromium on the level of IL-12 and IFN-gamma in occupationally exposed workers.
ABSTRACT Chromium may affect humoral and cellular immunity, acting on T lymphocytes as well as on granulocytes and monocytes cells. Cytokines play an important role in the immune balance. In this study, the level of IL-12 and IFN-gamma were evaluated in the sera and PHA/LPS stimulated culture supernatant of human PBMCs of healthy volunteers and occupationally exposed chromium workers. All the workers were highly exposed to chromium having mean of 104.65+/-77.21 microg/dL (range 23.7-316.8 microg/dL). A suspension of exposed and unexposed human PBMC (0.5x10(6) cells/ml) prepared and cultured in RPMI-1640 supplemented with 10% FCS for 18 h in the presence or absence of LPS (10 ng/ml) which used for stimulation of IL-12 and IFN-gamma. The level of IL-12 and IFN-gamma were evaluated in the sera samples as well as LPS stimulated and unstimulated culture supernatant of h-PBMCs of chromium exposed workers. In these chromium exposed workers the level of IL-12 was 433.66+/-197.49 pg/ml and 983.45+/-330.99 pg/ml in LPS stimulated culture supernatant of normal individuals and highly chromium exposed workers, which was significant (P<0.05). Although the level of IL-12 was (78.61+/-61.03 pg/ml to 146.52+/-46.37 pg/ml) elevated in unstimulated culture supernatant of h-PBMCs of chromium exposed individuals as compared to control, but it was not significant. This observation also suggests that a significant increase in IFN-gamma production in LPS stimulated and unstimulated culture supernatant of h-PBMCs of chromium exposed workers as compared to control. However, IFN-gamma level have a significant positive correlation between blood chromium level (r=0.833, t=6.3872, P 0.05) and exposure time (in years) (r=0.8916, t=8.3540, P 0.05) of the occupationally exposed workers.
- [show abstract] [hide abstract]
ABSTRACT: Genetically mercury-susceptible (H-2s) mice in which the nude (athymic) mutation had been introduced, and euthymic (H-2s) mice treated with anti-CD4 monoclonal antibodies were used to determine the importance of T-helper (CD4+) cells for induction of autoimmunity by mercury, and to study the possibility of using anti-CD4 MAb for treatment of manifest autoimmunity. SJL/N and (A.SW x SJL-nu) F1 x SJL-nu BC (H-2s) mice homozygous for the nude mutation (nu/nu) were treated with 10 mg HgCl2/litre drinking water for 6 weeks. These mice developed neither the antinucleolar antibodies (ANoA) nor the systemic immune-complex (IC) deposits seen in mercury-treated littermates heterozygous for the nude mutation (nu/+). The nu/nu mice showed a significant and substantial reduction of splenocytes with pan-T-(CD3+), T-helper-(CD4+) and T-cytotoxic/suppressor (CD8+) markers, which was accompanied by a severe reduction of the proliferative response to Concanavalin A. Euthymic SJL/N mice given an initial intravenous (i.v.) injection of 100 micrograms anti-CD4 MAb (clone GK 1.5, rat IgG2b), followed by 6 weeks treatment with 100 micrograms anti-CD4 MAb intraperitoneally (i.p.) every third day in combination with 10 mg HgCl2/litre drinking water, did not develop ANoA or systemic IC-deposits. These features were seen in controls i.p. injected with rat IgG2b and given HgCl2 in the drinking water. The anti-CD4 MAb-treated mice showed very few CD4+ splenocytes, but a significant increase of CD8+ cells and severely impaired T-cell function. The possibility of treating longstanding autoimmune conditions with anti-CD4 MAb was examined by giving euthymic SJL mice HgCl2 for 3 months, followed by a mercury-free interval of 3 months and finally 7 weekly injections of 1 mg anti-CD4 MAb. This therapy caused a severe reduction of CD4+ cells, but there was no decline in the ANoA titre. In conclusion, induction of systemic autoimmunity by mercury was strictly dependent on T cells, specifically T-helper (CD4+) cells, and mercury-induced ANoA persisted for a long time after stopping mercury treatment. At this late stage, the autoimmune condition was no longer amenable for anti-CD4 MAb therapy.Journal of Autoimmunity 01/1996; 8(6):809-23. · 8.15 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: All prostheses with metallic components release metal debris that can potentially activate the immune system. However, implant-related metal hyper-reactivity has not been well characterized. In this study, we hypothesized that adaptive immunity reaction(s), particularly T-helper type 1 (Th1) responses, will be dominant in any metal-reactivity responses of patients with total joint replacements (TJAs). We tested this hypothesis by evaluating lymphocyte reactivity to metal "ions" in subjects with and without total hip replacements, using proliferation assays and cytokine analysis. Lymphocytes from young healthy individuals without an implant or a history of metal allergy (Group 1: n = 8) were used to assess lymphocyte responses to metal challenge agents. In addition, individuals (Group 2: n = 15) with well functioning total hip arthroplasties (average Harris Hip Score = 91, average time in-situ 158 months) were studied. Age matched controls with no implants were also used for comparison (Group 3, n = 8, 4 male, 4 female average age 70, range 49-80). Group 1 subjects' lymphocyte proliferation response to Aluminum+3, Cobalt+2, Chromium+3, Copper+2, Iron+3, Molybdenum+5, Manganeese+2, Nickel+2, Vanadium+3 and Sodium+2 chloride solutions at a variety of concentrations (0.0, 0.05, 0.1, 0.5, 1.0 and 10.0 mM) was studied to establish toxicity thresholds. Mononuclear cells from Group 2 and 3 subjects were challenged with 0.1 mM CrCl3, 0.1 mM NiCl2, 0.1 mM CoCl2 and approx. 0.001 mM titanium and the reactions measured with proliferation assays and cytokine analysis to determine T-cell subtype prominence. Primary lymphocytes from patients with well functioning total hip replacements demonstrated a higher incidence and greater magnitude of reactivity to chromium than young healthy controls (p < 0.03). Of the 15 metal ion-challenged subjects with well functioning total hip arthroplasties, 7 demonstrated a proliferative response to Chromium, Nickel, Cobalt and/or Titanium (as defined by a statistically significant >2 fold stimulation index response, p < 0.05) and were designated as metal-reactive. Metals such as Cobalt, Copper, Manganese, and Vanadium were toxic at concentrations as low as 0.5 mM while other metals, such as Aluminum, Chromium, Iron, Molybdenum, and Nickel, became toxic at much higher concentrations (>10 mM). The differential secretion of signature T-cell subsets' cytokines (Th1 and Th2 lymphocytes releasing IFN-gamma and IL-4, respectively) between those total hip arthroplasty subjects which demonstrated metal-reactivity and those that did not, indicated a Th1 type (IFN-gamma) pro-inflammatory response. Elevated proliferation and production of IFN-gamma to metals in hip arthroplasty subjects' lymphocytes indicates that a Th1 (vs. Th2) type response is likely associated with any metal induced reactivity. The involvement of an elevated and specific lymphocyte response suggests an adaptive (macrophage recruiting) immunity response to metallic implant debris rather than an innate (nonspecific) immune response.Journal of Orthopaedic Surgery and Research 01/2008; 3:6. · 1.01 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: CD4 helper T cells can be divided into Th1 and Th2 subsets based upon the cytokines they produce. Th1 and Th2 cells have been found to be mutually antagonistic, leading to either Th1- or Th2-dominated responses upon immunization. In recent years, several authors have suggested that in chronic inflammatory autoimmune diseases such as diabetes, multiple sclerosis and rheumatoid arthritis, Th1 cells are pathogenic and Th2 cells are protective. Therefore, a successful deviation from a Th1-dominated to a Th2-dominated response could have clinical benefits for individuals suffering from these diseases. Unfortunately, data accumulated over recent years have not supported this approach, in particular regarding the protective role of Th2 cells. In this review we discuss these data and conclude that, at least using currently available tools, immune deviation from Th1 to Th2-dominated responses is ineffective unless started at very early (subclinical) stages of the disease. In addition, we examine some recent data suggesting that, under some circumstances, Th2 cells can be pathogenic.Cytokine & Growth Factor Reviews 07/1998; 9(2):139-51. · 8.83 Impact Factor