In vivo modulation of cytokine synthesis by intravenous immunoglobulin.
We examined the effects of intravenous immunoglobulin (IVIG) on cytokine regulation in vivo using samples taken before and after replacement-dose (200-400 mg/kg) IVIG in a group of patients with common variable immunodeficiency (CVID) and X-linked agammaglobulinaemia (XLA). The intracellular cytokine content of CD4+ and CD8+ lymphocytes, and their CD28+/- subsets, were measured following in vitro activation with phorbol myristate acetate (PMA) and ionomycin. The cytokines IL-2, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha), and the early activation marker CD69, were assessed by four-colour flow cytometry of whole blood cultures taken before and after IVIG infusion. There was a significant increase in IL-2 expression in CD4+ (and CD4+28-) cells and an increase in TNF-alpha expression in CD8+28- cells following IVIG in CVID, but not in XLA patients. IFN-gamma and CD69 expression were not affected by IVIG infusion. This increase in TNF-alpha and IL-2, combined with unchanged IFN-gamma expression, is evidence against the putative 'anti-inflammatory' role of IVIG, and may explain the failure of resolution of granulomata in CVID patients treated with IVIG alone.
Sewell
W A
WA
MRC Immunodeficiency Research Group, Department of Immunology, Royal Free & UC Medical School, Royal Free Campus, London, UK.
North
M E
ME
Cambronero
R
R
Webster
A D
AD
Farrant
J
J
D000328:Adult; D000361:Agammaglobulinemia / Q000235:genetics / Q000276:immunology / Q000628:therapy; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D017074:Common Variable Immunodeficiency / Q000276:immunology / Q000628:therapy; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage*; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014960:X Chromosome / Q000235:genetics
D016207:Cytokines; D016756:Immunoglobulins, Intravenous; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma