INCREASED LIPID-PEROXIDATION AND DECREASED ANTIOXIDANTS IN LUNGS OF GUINEA-PIGS FOLLOWING AN ALLERGIC PULMONARY RESPONSE

Oxygen-derived radicals and cytokines are known to play key roles in c ellular inflammation accompanying allergic lung disease. Using a well- characterized guinea pig model of pulmonary ovalbumin (OA) hypersensit ivity, we studied lipid peroxidation and endogenous antioxidant reserv e in bronchoalveolar lung fluid (BAL) following a severe pulmonary all ergic reaction. Since TNF-cr is known to be involved in oxygen radical generation, we also examined TNF production in response to antigen ch allenge, By 24 hr after antigen challenge, the number of eosinophils i n BAL was increased 3.5-fold compared with nonsensitized but challenge d control animals. Immunohistochemical evaluation of BAL cells, employ ing a polyclonal antibody to murine TNF-a, demonstrated the presence o f TNF in eosinophils. A 2.4-fold higher concentration of lipid peroxid ation products was found in BAL fluid of sensitized and challenged vs nonsensitized, challenged guinea pigs (p < 0.05), Endogenous antioxida nt levels were lower in the BAL fluid of the sensitized, challenged gu inea pigs. The concentration of the major lipid-soluble antioxidant, v itamin E, was 8.7-fold lower than that in nonsensitized controls (p < 0.001) and the endogenous reserve of water-soluble antioxidants (thiol s and ascorbic acid) was decreased 4-fold from that of control animals (p < 0.02). These results indicate an antioxidant/prooxidant imbalanc e associated with an allergic pulmonary episode. (C) 1995 Academic Pre ss, Inc.