IL-10-deficient B10.Q mice develop more severe collagen-induced arthritis,but are protected from arthritis induced with anti-type II collagen antibodies

IL-10 is a pleiotropic cytokine with stimulatory and inhibitory properties, and is thought to have a protective role in rheumatoid arthritis and colla gen-induced arthritis (CIA). In this study, we investigated how IL-10 defic iency affects CIA and anti-collagen type II (CII) Ab-transferred arthritis in C57BL/10.Q (B10.Q) mice. The B10.Q.IL-10(-/-) mice had an 8-cM 129/Ola f ragment around the IL-10 gene. The mice were treated with antibiotics, appe ared healthy, and had no colitis. T cells from IL-10(-/-) mice expressed si milar levels of IFN-gamma, IL-2, and IL-4 after mitogen stimulation; howeve r, macrophages showed a reduced TNF-alpha production compared with IL-10(+/ -) littermates. IL-10(-/-) mice had an increased incidence, and a more seve re CIA disease than the IL-10+/- littermates. To study the role of IL-10 in T cell tolerance, IL-10(-/-) were crossed into mice carrying the immunodom inant epitope, CII(256-270), in cartilage (MMC) or in skin (TSC). Both IL-1 0(-/-) and IL-10(+/-) MMC and TSC mice were completely tolerized against CI A, indicating that lack of IL-10 in this context did not break tolerance. T o investigate whether IL-10 was important in the effector phase of CIA, art hritis was induced with anti-CII Abs. Surprisingly, IL-10(-/-) were less su sceptible to Ab-transferred arthritis, as only 30% showed signs of disease compared with 90% of the littermates. Therefore, IL-10 seemed to have a pro tective role in CIA, but seemed to exacerbate the arthritogenicity of anti- CII Abs. These data emphasize the importance of studying IL-10 in a defined genetic context in vivo, to understand its role in a complex disease like arthritis.