Infliximab induces potent anti-inflammatory and local immunomodulatory activity but no systemic immune suppression in patients with Crohn's disease.
BACKGROUND
Anti-TNFalpha therapy with infliximab is effective for Crohn's disease. Infliximab neutralizes the biological activities of TNFalpha, a cytokine involved in host-defence against certain infections.


OBJECTIVE
To evaluate the effects of infliximab on the gut and peripheral immune system functions.


METHODS
Biopsies and blood samples from three clinical trials of infliximab in Crohn's disease were analysed. Pharmacokinetics, changes in leucocyte counts and T cell subsets, T cell function, and cytokine profiles of lamina propria mononuclear cells (LPMC) and peripheral blood mononuclear cells (PBMC) were analysed.


RESULTS
Infliximab has a serum half-life of 9.5 days and is still detectable in serum 8 weeks after infusion. Leucocyte counts showed consistent changes from baseline toward normal values after therapy. Monocytes and lymphocytes were modestly increased, while neutrophils were decreased 4 weeks after treatment. Lymphocyte subsets and T cell proliferative responses were not altered after therapy. The proportion of PBMCs capable of producing IFNgamma and TNFalpha did not change, while Th1 cytokine production by stimulated LPMC was decreased after infliximab therapy.


CONCLUSIONS
The clinical efficacy of infliximab is based on local anti-inflammatory and immunomodulatory effects in the bowel mucosa, without generalized suppression of systemic immune functions in Crohn's disease patients.
Cornillie
F
F
Centocor Inc., Malvern, PA, USA. cornillief@centocor.com
Shealy
D
D
D'Haens
G
G
Geboes
K
K
Van Assche
G
G
Ceuppens
J
J
Wagner
C
C
Schaible
T
T
Plevy
S E
SE
Targan
S R
SR
Rutgeerts
P
P
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D003424:Crohn Disease / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000032:analysis*; D004311:Double-Blind Method; D005765:Gastrointestinal Agents / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D000069285:Infliximab; D007413:Intestinal Mucosa / Q000276:immunology*; D018655:Lymphocyte Count; D009504:Neutrophils / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D016207:Cytokines; D005765:Gastrointestinal Agents; D000069285:Infliximab