Interleukin-5 modulates interleukin-8 secretion in eosinophilic inflammation.
Serum and BALF (bronchoalveolar lavage fluid) IL-8 levels and serum levels were investigated in Toxocara canis infected guinea-pigs and the role of IL-5 as a modulator of cytokine secretion was studied. Serum levels increased early in infected animals, exceeding control levels 4 h after infection, peaked between days 6 and 18, and continued to exceed control levels after 48 days of infection. Serum and BALF IL-8 levels showed the same profile as blood eosinophilia, increasing 6 days post-infection and peaking between days 18 and 24. Treatment of infected animals with anti-IL-5 Ab suppressed eosinophilia with a parallel increase in blood IL-8 levels, whereas no change was found in levels. To support our in vivo observation we carried out experiments in vitro using guinea-pig LPS-stimulated adherent peritoneal cells which release large amounts of IL-8 into the supernatants. When rIL-5 was added to LPS-stimulated cells, 65% inhibition of IL-8 release into the supernatants 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 are released concomitant with or after IL-5 in the eosinophilic inflammation induced by T. canis. Moreover, in addition to showing that IL-5 is fundamental for the induction of blood eosinophilia, the present results suggest that this cytokine may play a new biological role by acting as modulator of IL-8 secretion.
Faccioli
L H
LH
Department of Parasitology, Microbiology and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil. facciol@fmrp.usp.br
Medeiros
A I
AI
Malheiro
A
A
Pietro
R C
RC
Januário
A
A
Vargaftig
B B
BB
D000818:Animals; D000906:Antibodies / Q000378:metabolism; D001772:Blood Cell Count; D001992:Bronchoalveolar Lavage Fluid; D015536:Down-Regulation; D004804:Eosinophils / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005269:Femur / Q000378:metabolism; D006168:Guinea Pigs; D015848:Interleukin-5 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D017166:Toxocara canis / Q000276:immunology*; D014120:Toxocariasis / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000906:Antibodies; D015848:Interleukin-5; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha