THE DELAYED-TYPE HYPERSENSITIVITY REACTION IS DEPENDENT ON IL-8 - INHIBITION OF A TUBERCULIN SKIN REACTION BY AN ANTI-IL-8 MONOCLONAL-ANTIBODY

Cell-mediated immune reactions are essential to our immune response to ward foreign organisms such as microorganisms, or in the response towa rd foreign tissue Ags, as seen in the rejection of allogeneic transpla nted organs. Similar reactions form the basis for the development and the progression of delayed-type hypersensitivity (DTH) reactions. We f ound that the alpha-chemokine IL-8 plays an important pathophysiologic role for the development of a DTH reaction because infusion of a neut ralizing anti-IL-8 mAb (WS-4) was able to suppress the development of a tuberculin skin reaction in rabbits, as judged by histologic, bioche mical, and clinical examinations. Thus, the number of neutrophil granu locytes and lymphocytes at the site of tuberculin injection was decrea sed considerably, and the clinical signs of inflammation were suppress ed almost completely at 24 h after intracutaneous injection of tubercu lin, as judged by the size of the infiltrates. In contrast, we did not see any effect on the visible erythema of the skin. We found that the tissue content of myeloperoxidase (MPO), reflecting the number of inf iltrating neutrophils, was lowered significantly. Furthermore, immunoh istochemical analysis confirmed that IL-8 immunoreactivity is actually enhanced in the skin of positive tuberculin reactions. The results in dicate that IL-8 plays an important role for the early accumulation of leukocytes in the skin and for the clinical signs of a DTH reaction.