Fate of swallowed interleukin 8 and TNF alpha, and effect on the Wistar rat gut.
To evaluate the passage of cytokines through the gastrointestinal tract, we investigated the digestion of interleukin-8 (IL-8) and tumour necrosis factor alpha (TNF alpha), in vitro and in vivo, and their propensity to induce intestinal inflammation. We serially immuno-assayed IL-8 and TNF alpha solutions co-incubated with each of three pancreatin preparations at pH 4.5 and pH 8. We gavaged IL-8, TNF alpha and marker into 15 Wistar rats, and measured their faecal cytokine concentrations by ELISA and histologically examined their guts. IL-8 immunoreactivity was extinguished by all pancreatin preparations after 1 h of incubation at 37 degrees C. TNF alpha concentration progressively fell from 1 to 4 h with all enzyme preparations. Buffer control samples maintained their cytokine concentrations throughout incubation. No IL-8 or TNF alpha was detected in any rat faecal pellets. There was no significant proinflammatory effect of the gavaged cytokines on rat intestine. IL-8 and TNF alpha in aqueous solution could well be fully digested in the CF gut when transit time is normal and exogenous enzymes are provided, although cytokines swallowed in viscous sputum may be protected from such digestion.
Department of Gastroenterology and Nutrition, Royal Children's Hospital Brisbane, Herston, Queensland 4029, Australia. g.briars@doctors.org.uk
G L
GL
Briars
R M
RM
Greer
G J
GJ
Cleghorn
R W
RW
Shepherd
D000284:Administration, Oral; D000818:Animals; D016207:Cytokines / Q000008:administration & dosage / Q000276:immunology*; D004063:Digestion / Q000276:immunology; D005243:Feces / Q000737:chemistry; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000276:immunology; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000276:immunology*; D005772:Gastrointestinal Transit / Q000276:immunology; D006801:Humans; D016209:Interleukin-8 / Q000008:administration & dosage / Q000276:immunology*; D008297:Male; D010194:Pancreatin / Q000008:administration & dosage / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D013183:Sputum / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000276:immunology*
D016207:Cytokines; D005765:Gastrointestinal Agents; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D010194:Pancreatin