Article

The association of luteinizing hormone and follicle-stimulating hormone with cytokines and markers of disease activity in rheumatoid arthritis: a case-control study

Department of Rheumatology, Betanien Hospital, Skien, Norway.
Scandinavian journal of rheumatology (Impact Factor: 2.61). 03/2010; 39(2):109-17. DOI: 10.3109/03009740903270607
Source: PubMed

ABSTRACT Disease activity in rheumatoid arthritis (RA) varies substantially during periods when luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels change, for example during pregnancy, postpartum, and menopause. We wanted to investigate whether small fluctuations in these hormones could be associated with similar fluctuations in cytokines and disease activity in RA.
Disease activity markers, serum LH, FSH, and 24 cytokines were assessed on days 1 and 8 in 20 RA patients (median age 58 years, six males) and 19 controls (median age 56 years, six males).
Percentage changes in LH and FSH correlated positively with percentage changes in key proinflammatory cytokines such as tumour necrosis factor (TNF)alpha (LH r = 0.737, p = 0.0007; FSH r = 0.680, p = 0.001) and interleukin (IL)-1beta (LH r = 0.515, p = 0.050; FSH r = 0.749, p = 0.0008). Similar correlations were observed with IL-2, IL-2R, IL-8, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and eotaxin, but not with the anti-inflammatory cytokine IL-10, in RA and not in controls. Percentage changes in LH, FSH, and cytokines were not correlated with percentage changes of several disease activity markers but were correlated positively with cross-sectional levels of disease activity markers [erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Visual Analogue Scale (VAS) pain, VAS global (physician/patient), and the modified Health Assessment Questionnaire (MHAQ)].
The significant associations between percentage changes in LH and FSH and percentage changes in key cytokines and several cross-sectional markers of disease activity may indicate that LH and FSH influence crucial points of the cytokine cascade in RA. This may help to explain, partially, why disease activity initiates or worsens during periods of increased LH and FSH, such as the postpartum period and the menopause.

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    • "Gonadotropins can regulate production of TNF, which was shown to alter cell cycle dynamics by the group that first described it (Darzynkiewicz et al., 1984). In brief, FSH has been reported to induce TNF in vitro (Iqbal et al., 2006), and high LH and FSH levels have allowed the rationalization, through their association with high TNF and IL-1␤, of the onset or exacerbation of rheumatoid arthritis in women at menopause (Kåss et al., 2010). As we have noted (Clark and Atwood, 2011), the antigonadotropic actions of leuprolide render it an anti-mitotic and anti-inflammatory agent when used to treat endometriosis . "
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    • "Gonadotropins can regulate production of TNF, which was shown to alter cell cycle dynamics by the group that first described it (Darzynkiewicz et al., 1984). In brief, FSH has been reported to induce TNF in vitro (Iqbal et al., 2006), and high LH and FSH levels have allowed the rationalization, through their association with high TNF and IL-1␤, of the onset or exacerbation of rheumatoid arthritis in women at menopause (Kåss et al., 2010). As we have noted (Clark and Atwood, 2011), the antigonadotropic actions of leuprolide render it an anti-mitotic and anti-inflammatory agent when used to treat endometriosis . "
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    • "Evidence for a role of gonadotropins in regulating TNF expression is demonstrated by the ability of FSH to induce TNF expression in investigations into the illness caused by chronic kidney dialysis [70]. Others, studying the reasons for the exacerbation of rheumatoid arthritis at the onset of menopause, have correlated the high circulating FSH and LH seen at this time with increases in TNF, interleukin-1␤ (IL-1␤) and monocyte chemoattractant protein (MCP)-1 [71]. These data are consistent with the anti-gonadotropic actions of leuprolide rendering it an anti-mitotic and anti-inflammatory agent when it is used to treat endometriosis. "
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