Interleukin-5 modulates interleukin-8 secretion in eosinophilic inflammation

SERUM and BALF (bro nch oalveolar lavage fluid) IL-8 leve ls and ser um le vels w e re in vestigated in To x o c a r a c a nis in fe cte d guin e a-pigs an d the ro le o f IL-5 as a m odulato r o f cytokin e se cr etion w as studie d. Serum leve ls in cr eased e arly in in fe cte d an im als, ex cee din g con tr ol leve ls 4 h afte r in fe ction , p eaked betw e en days 6 and 18, and con tin ue d to ex cee d con tro l leve ls afte r 48 days of in fe ction . Serum an d BALF IL-8 leve ls sh ow ed th e sam e p r ofile as blo od eo sin o ph ilia, in cr easin g 6 days p ost-in fe ction an d p e akin g betw e en days 18 an d 24. Tr eatm e nt o f in fe cte d an im als w ith an ti-IL-5 Ab s upp re sse d eo sin o p hilia w ith a p aralle l in cr ease in blood IL-8 levels , w h er eas no ch an ge w as fo un d in le vels. To sup po rt our in vivo o bs e rvation w e carrie d o ut ex p er im en ts in vitro usin g guin ea-pig LPSstim ulate d adh er en t p e rito ne al ce lls w h ic h r ele ase lar ge am o un ts of IL-8 in to th e sup er natants. Wh en rIL-5 w as adde d to LPS-stim ulated ce lls, 65% in hibition o f IL-8 re lease in to th e supe r natants w as observ ed. Pr e-in cubatio n o f cells w ith anti-IL-5 Ab p r eve nted th e in h ibitio n o f IL-8 r elease in to the supe r natants in duce d by rIL-5. Our r es ults de m on strate fo r th e firs t tim e th at TNF-a an d IL-8 are r eleased co ncom itan t w ith or afte r IL-5 in th e eos in o p hilic in flam m atio n in duce d by T. c a nis . Mor eo ver, in addition to sho w in g that IL-5 is fundam e ntal for the in duction o f bloo d eo sin o ph ilia, th e p re sen t r es ults suggest th at th is cytokin e m ay p lay a ne w biological r ole by actin g as m o dulato r o f IL-8 secr etion .