The immunomodulatory properties of in vitro immunoglobulins are dose-dependent.
OBJECTIVE
The mechanism by which intravenous immunoglobulins (immunoglobulin G, IgG) exert their beneficial effect on multiple sclerosis (MS) is unknown. Furthermore, there is uncertainty about the optimal dosage of IgG. Therefore, we investigated the influence of different IgG dosages on cytokine production in MS.


METHODS
Twenty-five MS patients and 15 healthy controls were enrolled. We measured the production of interferon gamma (IFN-gamma), tumour necrosis factor alpha (TNF) and interleukin 10 (IL-10) in peripheral blood lymphocytes by flowcytometry after stimulation without and with IgG in different doses (1, 5 and 10 mg/ml).


RESULTS
IFN-gamma and TNF were decreased significantly (P = 0.001) in the untreated and interferon beta (IFN-beta) treated patients after stimulation with IgG. In contrast, IL-10 production was significantly enhanced (P = 0.001) at least in the untreated patient group. The reduction of the pro-inflammatory cytokines IFN-gamma and TNF after stimulation with different IgG doses was clearly dose-dependent in all groups.


CONCLUSIONS
Besides a suppression of the pro-inflammatory cytokines IFN-gamma and TNF, IgG enhances the anti-inflammatory cytokine IL-10. This effect is dose-dependent, speaking in favour of higher IgG doses in the treatment of MS.
Reske
D
D
Department of Neurology, University of Cologne, Cologne, Germany.
Schoppe
S
S
Broicher
C
C
Petereit
H-F
HF
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000627:therapeutic use*; D000328:Adult; D000970:Antineoplastic Agents / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000627:therapeutic use*; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000737:chemistry* / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma