INTERLEUKIN-5 MODULATES INTERLEUKIN-8 SECRETION IN EOSINOPHILIC INFLAMMATION

SERUM and BALF (bronchoalveolar lavage fluid) IL-8 levels and serum le vels were investigated in Toxocara canis infected guinea-pigs and the role of IL-5 as a modulator of cytokine secretion was studied. Serum l evels increased early in infected animals, exceeding control levels 4 h after infection, peaked between days 6 and 18, and continued to exce ed control levels after 48 days of infection. Serum and BALF IL-8 leve ls showed the same profile as blood eosinophilia, increasing 6 days po st-infection and peaking between days 18 and 24. Treatment of infected animals with anti-IL-5 Ab suppressed eosinophilia with a parallel inc rease in blood IL-8 levels, whereas no change was found in levels. To support our in vivo observation we carried out experiments in vitro us ing guinea-pig LPS-stimulated adherent peritoneal cells which release large amounts of IL-8 into the supernatants. When rIL-5 was added to L PS-stimulated cells, 65% inhibition of IL-8 release into the supernata nts was observed. Pre-incubation of cells with anti-IL-5 Ab prevented the inhibition of IL-8 release into the supernatants induced by rIL-5. Our results demonstrate for the first time that TNF-alpha and IL-8 ar e released concomitant with or after IL-5 in the eosinophilic inflamma tion induced by T. canis. Moreover, in addition to showing that IL-5 i s fundamental for the induction of blood eosinophilia, the present res ults suggest that this cytokine may play a new biological role by acti ng as modulator of IL-8 secretion.