Activated polymorphonuclear leukocytes (PMNL) might be an important source of host tissue damage. PMNL may be primed by various inflammatory mediators for an increased production of reactive oxygen species (ROS). The short-term priming effects of two cytokines, interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), on rat PMNL in whole unfractionated blood were investigated in the present study. Incubation of PMNL with cytokine alone did not induce the detectable ROS production without addition of a second stimulus-phorbol myristate acetate (PMA) or opsonized zymosan particles (OZP). One-hour incubation with TNF-alpha, or the mixture of TNF-alpha + IFN-gamma resulted in a dose-dependent enhancement of ROS production in response to PMA. Moreover, the incubation with both IFN-gamma and TNF-alpha caused a significantly higher increase of ROS production than with TNF-alpha alone. However, no priming effects of IFN-gamma on the PMA-induced ROS production were observed. Finally, none of the cytokines enhanced the total production of ROS upon the stimulation with OZP, although changes in the time course of ROS production were observed. Thus, different signal transduction pathways seem to be involved in PMA- and OZP-induced respiratory burst. Alternatively, partial activation and assembling of NADPH oxidase during cytokine treatment might explain the differences observed between PMA- and OZP-induced ROS production. The results of the present study suggest that IFN-gamma may enhance the priming effects of TNF-alpha. This finding may have implications for understanding the mechanisms by which both cytokines may contribute to PMNL-mediated tissue injury during various clinical conditions, as well as to host defense against invading pathogens.

Department of Comparative Animal Physiology and General Zoology Faculty of Science Masaryk University Brno Czech Republic