Differential effect of severe and moderate social stress on blood immune and endocrine measures and susceptibility to collagen type II arthritis in male rats.

The effects of social stress on several blood immune measures and collagen-induced arthritis (CIA) were investigated in Wistar rats using the resident-intruder confrontation paradigm to induce stress of different intensity. Male intruders were exposed for one week to a dominant opponent either repeatedly for 4h daily (moderate stress) or continuously (severe stress). Arthritis was induced by intradermal injection of collagen type II (CII) into the tail skin at the end of day 3 of confrontation. Only severe stress was associated with decreased CD4 and CD8 T cells, and the increase in granulocyte numbers and body mass loss was more pronounced under these conditions. Only severe stress reduced the susceptibility to arthritis by about 50%. Severity scores did not differ in the first five days after disease onset between all groups. Subsequent experiments focused on severely stressed rats indicated that disease progressed until day 10 only in control animals, but not in severely stressed males. Stressor exposure resulted in increased blood monocyte numbers, but these males failed to accumulate macrophages into the skin at the site of CII injection. High numbers of attacks experienced by intruders correlated with delayed disease onset in severely stressed rats. We hypothesize that severe stress persisting after disease induction exhibits beneficial effects on the susceptibility of CIA and propose that the specific endocrine and immunological profile associated with severe stress is an important factor for disease outcome--a factor which probably explains many of the conflicting data of previous stress studies on CIA.