High interleukin-10 production in first-degree relatives of patients with generalized but not cutaneous lupus erythematosus

Background: Preclinical research suggests that interleukin-10 (IL-10) is associated with susceptibility to and severity of systemic lupus erythematosus. Chronic cutaneous lupus erythematosus is thought to be immunogenetically different from systemic lupus erythematosus. We hypothesized that high innate production of IL-10 underlies systemic but not chronic cutaneous lupus erythematosus. Methods: IL-10 production was determined after endotoxin stimulation of whole-blood samples. In whole-blood samples, disease activity and medication influence the IL-10 production in patients. Therefore, healthy first-degree relatives of patients were evaluated. One hundred sixty-six first-degree relatives of patients with systemic lupus, 50 first-degree relatives of patients with chronic cutaneous lupus, and 133 control persons were studied. Innate IL-10 production of the patient was estimated as the mean IL-10 production of the unaffected relatives. Polymorphisms located -1082, -819, and -592 base pairs relative to the IL-10 gene were typed by allele-specific oligohybridization of polymerase chain reaction-amplified DNA fragments. Results: IL-10 production was higher in the families of patients with systemic lupus than in the control families (1517±94 vs 1180±59 pg/mL; P=0.003). IL-10 production in the families of patients with chronic cutaneous lupus was similar to that in control families (1216±82 vs 1180±59 pg/ml; P=0.74). IL-10 production was also similar in families of patients with severe compared with nonsevere systemic lupus (P=1.0). The frequency of -1082/-819/-592 haplotypes GCC, ACC, and ATA was similar among patients and compared with the control persons (P=0.29). Conclusions: High innate IL-10 production underlies susceptibility for systemic lupus erythematosus but not the severity of the disease. It is not related to chronic cutaneous lupus erythematosus.