MECHANISM OF PENTOXIFYLLINE MEDIATED DOWN-REGULATION OF KILLER LINEAGE CELL FUNCTIONS

THE authors reported recently that endotoxaemia mediated elevated leve ls of tumour necrosis factor (TNF-alpha) and interleukin-1 alpha (IL-1 alpha) were involved in the pathophysiology of acute heat stroke pati ents. Pentoxifylline (PTX) is known to modulate neutrophil functions. In the present study the effects of PTX on lipopolysaccharide (LPS) an d cytokine induced T-cell and macrophage (phi M) activation, and on na tural killer (NK) cell and lymphokine activated killer (LAK) cell medi ated cytotoxicity were examined. Finally, the effect of PTX on the exp ression of adhesion molecules (LFA-1, Mac-1 and ICAM-1), and cytokine (IL-1 alpha, IL-2, TNF-alpha IL-6 and IFN-gamma) production and their surface receptor expression in response to LPS activation was investig ated. PTX free cultures served as a control. Results revealed that PTX can down-regulate all the above-mentioned immunological parameters in a dose-dependent manner. These findings might have far reaching clini cal implications.