Modulating effects of intravenous immunoglobulins on serum cytokine levels in patients with primary hypogammaglobulinemia.
BACKGROUND
Intravenous immunoglobulins (IVIG) have usually been administered for replacement therapy of humoral immunodeficiencies, but their use in treating other disorders with an immune pathogenesis is increasing. The exact mechanism of action by which IVIG are of benefit in such diseases is complex and only partly understood. One of the proposed mechanisms of action is the modulation of cytokine release.


METHODS
We selected 29 patients with primary hypogammaglobulinemia (common variable immunodeficiency), receiving long-term substitutive therapy with IVIG, and 14 healthy blood donors as a control group. Blood samples were then taken before and 1 hour after finishing the IVIG infusion. Only one blood sample was obtained from the healthy controls. The cytokines studied were interleukin (IL)-1 beta, IL-1 receptor antagonist (IL-1Ra), IL-2, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma.


RESULTS
Patients with primary hypogammaglobulinemia showed significantly higher serum levels of IL-6, IL-8, IL-1Ra, and TNF alpha than healthy controls. IVIG infusion significantly increased serum concentration levels of IL-6, IL-8, IL-1Ra, and TNF alpha. No significant variation was observed in serum levels of IL-beta, IFN gamma, or IL-2 after IVIG infusion. Age, IVIG commercial preparation, and IVIG dose did not influence cytokine serum levels. Moreover, a significant correlation was observed between serum level variations of IL-1Ra and TNF alpha, as well as an associative trend between maximum changes in IL-6 and IL-8 concentrations.


CONCLUSIONS
IVIG administration significantly alters the serum pattern of selected cytokines, which might explain, at least in part, the mechanism of action of IVIG in autoimmune or inflammatory disorders.
Ibáñez
Cristina
C
Department of Pharmacy, Hospital Vall d'Hebron, Barcelona 119-129, Spain.
Suñé
Pilar
P
Fierro
Ana
A
Rodríguez
Santiago
S
López
Maite
M
Alvarez
Antonio
A
De Gracia
Javier
J
Montoro
José-Bruno
JB
D000328:Adult; D000361:Agammaglobulinemia / Q000188:drug therapy*; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000097:blood*; D007378:Interleukins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D016756:Immunoglobulins, Intravenous; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma