Complement activation in patients with congestive heart failure: effect of high-dose intravenous immunoglobulin treatment.
BACKGROUND
Increasing evidence implicates innate immunity in the pathogenesis of congestive heart failure (CHF). In the present study, we examined the possible role of complement, an important part of innate immunity, in CHF.


RESULTS
Complement activation was analyzed in systemic and coronary circulation in 39 patients with CHF and 20 healthy control subjects. In a double-blind, placebo-controlled study, we have recently reported that high-dose intravenous immunoglobulin (IVIG) improves left ventricular ejection fraction (LVEF) in these patients. To examine if this improvement was related to IVIG-induced effects on complement, we also examined complement activation during induction (first week) and maintenance therapy (6 months) with IVIG or placebo. Our main findings were: (1) We found enhanced systemic complement activation involving classic, alternative, as well as terminal pathway in patients with CHF compared with healthy control subjects. (2) Particularly enhanced complement activation was found in coronary sinus, representing venous drainage from the heart. (3) The systemic complement activation was further enhanced during IVIG but not during placebo therapy, particularly during induction therapy. (4) Although IVIG improved LVEF in patients with CHF, the degree of IVIG-mediated complement activation was negatively correlated with this improvement of LVEF.


CONCLUSIONS
This study further supports the involvement of innate immunity in the pathogenesis of CHF. Our findings suggest that complement may be added to the list of possible therapeutic targets in CHF and that future studies with specific complement inhibitors may be of interest in this disorder.
Aukrust
P
P
Section of Clinical Immunology and Infectious Diseases, Research Institute for Internal Medicine, Rikshospitalet, University of Oslo, Norway. pal.aukrust@rikshospitalet.no
Gullestad
L
L
Lappegård
K T
KT
Ueland
T
T
Aass
H
H
Wikeby
L
L
Simonsen
S
S
Frøland
S S
SS
Mollnes
T E
TE
D002097:C-Reactive Protein / Q000187:drug effects / Q000378:metabolism; D003167:Complement Activation / Q000187:drug effects; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012850:Sinus of Valsalva / Q000276:immunology; D013318:Stroke Volume / Q000187:drug effects
D016756:Immunoglobulins, Intravenous; D002097:C-Reactive Protein