Lipopolysaccharide and a social stressor influence behaviour, corticosterone and cytokine levels: divergent actions in cyclooxygenase-2 deficient mice and wild type controls.

Administration of the endotoxin, lipopolysaccharide (LPS) diminished motor activity and increased plasma corticosterone as well as circulating levels of interleukin-1beta (IL-1beta), IL-6, tumor necrosis-factor-alpha (TNF-alpha) and IL-10. Among cyclooxygenase-2 (COX-2) knockout mice the behavioural, corticosterone and cytokine variations promoted by LPS were moderately (home cage activity, corticosterone, TNF-alpha) or largely (IL-6) reduced. However, if mice were exposed to a psychosocial stressor (social disruption associated with grouping mice with novel cage-mates after a period of isolation) coupled with LPS treatment, then the effects of the COX-2 deletion were absent, or there was a synergistic or additive elevation apparent (e.g., in the case of TNF-alpha, IL-6 and corticosterone). Evidently, COX-2 deletion may have either pro- or anti-inflammatory actions, depending upon the psychosocial context in which immune activation occurs.