Infliximab modifies mesenteric adipose tissue alterations and intestinal inflammation in rats with TNBS-induced colitis.
OBJECTIVE
Infliximab is a monoclonal anti-TNF-α antibody that is used therapeutically to treat Crohn's disease (CD). High levels of pro-inflammatory cytokines, especially TNF-α, have been observed in the gastrointestinal tract of CD patients and were associated with alterations in the mesenteric adipose tissue, which also contributed to the high levels of adipokine release. The authors used a rat model of colitis that produces mesenteric adipose tissue alterations that are associated with intestinal inflammation to study the effects that infliximab treatment has on adipokine production, morphological alterations in adipose tissue and intestinal inflammation.


METHODS
The ability of infliximab to neutralize rat TNF-α was evaluated in vitro using U937 cells. Colitis was induced by repeated intracolonic trinitrobenzene sulfonic acid instillations and was evaluated by macroscopic score, histopathological analysis, myeloperoxidase activity, TNF-α and IL-10 expression as well as iNOS (inducible NO synthase) expression and JNK phosphorylation in colon samples. The alterations in adipose tissue were assessed by TNF-α, IL-10, leptin, adiponectin and resistin levels as well as adipocyte size and peroxisome proliferator-activated receptor (PPAR)-γ expression.


RESULTS
Infliximab treatment controlled intestinal inflammation, which reduced lesions and neutrophil infiltration. Inflammatory markers, such as iNOS expression and JNK phosphorylation, were also reduced. In mesenteric adipose tissue, infliximab increased the production of IL-10 and resistin, which was associated with the restoration of adipocyte morphology and PPAR-γ expression.


CONCLUSIONS
Our results suggest that infliximab could contribute to the control of intestinal inflammation by modifying adipokine production by mesenteric adipose tissue.
Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, Bragança Paulista, SP, Brazil.
Thayane Rodrigues Leite
TR
Clemente
Aline Noronha
AN
Dos Santos
José Narciso
JN
Sturaro
Erica Martins Ferreira
EM
Gotardo
Caroline Candida
CC
de Oliveira
Simone Coghetto
SC
Acedo
Cintia Rabelo E Paiva
CR
Caria
José
J
Pedrazzoli
Marcelo Lima
ML
Ribeiro
Alessandra
A
Gambero
D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D000069285:Infliximab; D016753:Interleukin-10 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008643:Mesentery; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000378:metabolism; D047495:PPAR gamma / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D052243:Resistin / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D020298:U937 Cells
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D047495:PPAR gamma; D012333:RNA, Messenger; D052243:Resistin; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D014302:Trinitrobenzenesulfonic Acid; D000069285:Infliximab; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D048031:JNK Mitogen-Activated Protein Kinases