Associations between Smoking and Systemic Lupus Erythematosus (SLE)-Related Cytokines and Chemokines among US Female Nurses.

BACKGROUND Smoking has been associated with increased systemic lupus erythematosus (SLE) risk, but the biologic basis for this association is unknown. We investigated whether women's smoking was positively associated with SLE-associated pro-inflammatory chemokines/cytokines, [stem cell factor (SCF), B-lymphocyte stimulator (BLyS), interferon-inducible protein-10 (IP-10), interferon-alpha (IFN-α)]; or negatively associated with anti-inflammatory cytokine interleukin-10 (IL-10)]; and whether associations were modified by SLE-related autoantibody status. METHODS The Nurses' Health Study (NHS, n=121,700) and NHSII (n=116,429) cohorts were begun in 1976 and 1989. In 1988-1990 (NHS) and 1996-1999 (NHSII), ~25% participants donated blood samples. We identified 1177 women without SLE with banked samples and tested by ELISA for chemokines/cytokines as well as anti-Sm, -Ro/SSA, La/SSB and RNP. Antinuclear antibodies (ANA) were detected by HEp-2 cell indirect immunofluorescence and anti-double-stranded DNA antibodies and were assayed by ELISA. Smoking was assessed until blood draw. Separate tobit and linear regression analyses, adjusted for potential confounders, modeled associations between smoking and log-transformed chemokine/cytokine concentrations. Analyses were stratified by autoantibody status. Effect estimates were calculated as ratios of geometric means, expressed as % differences. RESULTS Among the 15% current/recent vs. 85% past/never smokers, BLyS levels were 8.7% higher (p<0.01), and were 24% higher (p<0.0001) among those ANA+. Current/recent smokers had IL-10 concentrations 46% lower (p<0.01) than past/never smokers; each 10 pack-years of smoking was associated with -17% IL-10 (p <0.001). Smoking was not associated with IP-10 or SCF. CONCLUSIONS Elevated BLyS and lower IL-10 levels among current smokers, particularly among ANA+ women, may be involved in SLE pathogenesis.