Anti-inflammatory trials in chronic heart failure.
Chronic heart failure (CHF) is accompanied by a dysregulated cytokine network, which is characterized by a rise in inflammatory cytokines and an inadequate elevation of anti-inflammatory mediators. This dysregulation has been implicated in the development and progression of CHF and, in the last decade, attempts have been made to modulate this imbalance in the cytokine network. With the exception of one larger mortality/morbidity study, all studies of immunomodulatory therapy in HF conducted to date have included <100 patients and the overall experience in this therapeutic area is limited compared with studies of neurohormonal antagonists, which have included several thousand patients. While trials of anti-tumor necrosis factor therapies have thus far failed, recent studies of broad-based immunomodulatory agents (e.g. intravenous immunoglobulin, thalidomide, and pentoxifylline) highlight a potential for such therapy in HF patients, in parallel with optimal cardiovascular treatment regimens. In addition to identifying the crucial factors in the immunopathogenesis of CHF in order to develop novel immunomodulatory treatment strategies, there is a clear need to confirm the results of the smaller studies conducted to date with larger placebo-controlled mortality studies that involve a diverse group of patients, with regard to the cause and severity of HF.
Aukrust
Pål
P
Research Institute for Internal Medicine, Rikshospitalet University Hospital, University of Oslo, Oslo, Norway. pal.aukrust@rikshospitalet.no
Yndestad
Arne
A
Ueland
Thor
T
Damås
Jan Kristian
JK
Gullestad
Lars
L
D000328:Adult; D000368:Aged; D000818:Animals; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D016166:Free Radical Scavengers / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007155:Immunologic Factors / Q000627:therapeutic use*; D007164:Immunosorbents / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010431:Pentoxifylline / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D013792:Thalidomide / Q000494:pharmacology; D016896:Treatment Outcome
D016207:Cytokines; D016166:Free Radical Scavengers; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D007164:Immunosorbents; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D013792:Thalidomide; D010431:Pentoxifylline