Signal transduction in inflammatory processes, current and future therapeutic targets: A mini review

The selective control of inflammatory reactions will continue to be a major issue in the development of new drugs. Many new molecular targets are comi ng up. This paper highlights a few key mediators that are nowadays consider ed as interesting therapeutic intervention points. Cytokines play an import ant regulatory role in the initiation, maintenance and termination of infla mmatory reactions. More than 50 cytokines have been identified, and more an d more has become known about their receptors and signal transduction pathw ays, Tumour necrosis factor-alpha (TNF-alpha) is still regarded as one of t he initial cytokines of the cascade, and different approaches are followed to control its synthesis, release or effects. Lipopolysaccharide(LPS) Is a one of the triggers that is able to induce a strong TNF-response. Inhibitor s of cyclic nucleotide phosphodiesterases (PDEs), including rolipram and pe ntoxifylline suppress the LPS-induced TNF-alpha production in monocytes/ ma crophages. In our laboratory it has been shown that the alternative way to increase cAMP levels, via stimulation of beta-adrenergic receptors, also pr ovides an effective way, both in vitro and in vivo, to inhibit TNF- alpha r elease. Other therapeutic ways include the use of antibodies directed to cy tokines, TNF receptor fused to IgG, antibody therapy against TNF, the use o f MAP kinase inhibitors. The different signal transduction pathways, includ ing the NF-kappa B activation route may provide alternative pharmacological tools. We may surely expect anti-inflammatory drugs of much greater specificity to be developed in the next decade. Despite the relative limited investments in veterinary drug development this will also have consequences for veterin ary therapy.