[Anti-cytokine therapy for severe acute pancreatitis].
The systemic manifestations of acute pancreatitis (AP) are responsible for the majority of pancreatitis-associated morbidity and mortality. Recent studies have established that severe AP is a disease with systemic inflammatory response syndrome as well as compensatory anti-inflammatory response syndrome. Based on their roles in the pathogenesis of AP, new therapies have been sought and tested, including those preventing the biological activity of two pro-inflammatory cytokines, tumor necrosis factor (TNF)-alpha and interleukin-1 (IL-1). Biological activity of TNF might be blunted by anti-TNF-alpha antibody or soluble TNF receptor, and IL-1 receptor antagonist might blunt that of IL-1. Although anti-cytokine therapies against IL-1, TNF-alpha or macrophage migration inhibitory factor showed promising results in experimental models of AP, the question remains as to whether similar antagonism during clinical pancreatitis would benefit patients with severe AP. Major considerations include the suitability of AP to cytokine antagonism in clinical settings, the possibility that such a therapy may lead to the development of immunosuppression and consequent infection, and whether a therapeutic window for such antagonism
Masamune
Atsushi
A
Division of Gastroenterology, Tohoku University Graduate School of Medicine.
Shimosegawa
Tooru
T
D000208:Acute Disease; D000068879:Adalimumab; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D004195:Disease Models, Animal; D015195:Drug Design; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors*; D000069285:Infliximab; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D008263:Macrophage Migration-Inhibitory Factors / Q000627:therapeutic use; D010195:Pancreatitis / Q000188:drug therapy* / Q000209:etiology; D011759:Pyrrolidines / Q000627:therapeutic use; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012720:Severity of Illness Index; D013859:Thiocarbamates / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D018836:Inflammation Mediators; D007375:Interleukin-1; D008263:Macrophage Migration-Inhibitory Factors; D011759:Pyrrolidines; D018124:Receptors, Tumor Necrosis Factor; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; C020972:pyrrolidine dithiocarbamic acid; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept