The role of cytokines and prostaglandin-E-2 in thymulin induced hyperalgesia

We have recently reported that intraperitoneal (i.p.) injection of thymulin at low doses (50 ng) resulted in thermal and mechanical hyperalgesia and u pregulation of the level of interleukin-1 beta in the liver. In this study, we demonstrate that such injections of thymulin result in a significant el evation in the levels of TNF-alpha (P<0.01) NGF (P<0.01) and PGE(2) (P<0.01 ) in the liver of the treated rats, in addition to the increase in the leve ls of IL-1 beta. Pretreatment with specific antagonists to each of these fa ctors (polyclonal anti-TNF-alpha, anti-NGF antiserum and IL-1 receptor anta gonist) did not result in the abolition of the hyperalgesia as assessed by the paw pressure, hot plate, paw immersion and tail flick tests. However, p retreatment with a combination of the above antagonist and antisera almost completely prevented thymulin-induced hyperalgesia. The cyclooxygenase inhi bitor, meloxicam, reversed in a dose dependent manner (0.2, 0.4 and 2 mg/kg ) thymulin effects as assessed by the different pain tests. It also abolish ed the thymulin-induced increase in the level of cytokines and NGF in the l iver. Our results indicate that PGE(2) could be the key mediator of the hyp eralgesic action of thymulin and the observed upregulation of proinflammato ry cytokines and NGF. (C) 2000 Elsevier Science Ltd. All rights reserved.