Background: We previously showed that the prevalence of allergic disease is decreased in patients with multiple sclerosis (MS); however, the mechanisms that explain this finding have not previously been defined. Objectives: We have demonstrated that protection of patients with MS from allergic disease may be caused by the production in monocytes from these patients of elevated quantities of IL-12 compared with that observed in monocytes from individuals with allergies. Methods: Purified monocytes from peripheral blood of subjects with or without allergies and from individuals with MS were directly stimulated with Staphylococcus aureus Cowan strain I in the absence of T cells. IL-12 was quantitated by a sensitive reverse transcription, competitive PCR. esults: IL-12 production was 5-fold greater in monocytes from patients with MS (n = 11) than that from individuals with allergies (n = 10) (for subjects with MS, 1.90 +/- 0.18 vs 1.24 +/- 0.19 log(10) fmol/mu L for individuals with allergies) (P =.02), Although the production of IL-12 in monocytes from patients with MS was slightly higher than that from subjects without allergies, this difference was not statistically significant. Conclusions: lL-12 production in individuals with MS is much greater than in individuals with allergies, Because IL-12 induces T-H1 cytokine synthesis and reduces the production of T-H2 cytokines, which amplify and prolong allergic inflammation, these studies suggest that enhanced IL-12 production may protect individuals with MS from the development of allergy but may predispose such individuals toward autoimmune inflammation in the central nervous system.