This is the 3/1/05 post from the same neurologist.
Avonex TH1 to TH2 shift may be key
IF Nbeta1a (Avonex/Rebif) cause a TH1 to TH2 shift. This is felt to be one of the good mechanisms in MS treatment. However, TH1 to TH2 shift may lead to PML...... THus there is a mechanism as to why combo could be worse than mono. Tysabri reduces the trafficking of activated lymphocytes into the brain
Clin Neurol Neurosurg. 2004 Jun;106(3):255-8. Related Articles, Links
IFN-beta1a and IFN-beta1b have different patterns of influence on cytokines.
Sega S, Wraber B, Mesec A, Horvat A, Ihan A.
Multiple sclerosis is characterized by elevated levels of proinflammatory cytokines produced by Th1 cells and decreased levels of anti-inflammatory cytokines produced by Th2 cells. IFN-beta treatment shifts the immune response from the Th1 to Th2 pattern, thus enhancing the production of anti-inflammatory Th2 cytokines such as IL-4, IL-10, and decreasing the production of proinflammatory Th1 cytokines such as IFN-gamma. To determine which IFN-beta has the stronger immunomodulatory effect we compared the levels of IL-4, IL-10, and IFN-gamma of 12 relapsing-remiting MS patients treated with IFN-beta1b (Betaferon) with those of 10 patients treated with IFN-beta1a (Avonex).
There were no statistically significant differences in duration of disease, number of relapses before and during treatment, and in EDSS after 2 years of treatment. After 1 year of treatment the concentration of IFN-gamma was significantly lower in the Betaferon group, and concentrations of IL-4 and IL-10 were significantly higher in the Avonex group. It appears that IFN-beta1b has a downregulatory effect on both Th1 and Th2 cytokines, while IFN-beta1a causes a shift of the cytokine profile toward the Th2 phenotype.
These two IFN have different influences on the pattern of cytokines in MS: IFN-beta1a enhances the production of anti-inflammatory cytokines IL-4 and IL-10 and IFN-beta1b decreases the production of the proinflammatory cytokine IFN-gamma.
PMID: 15177779 [PubMed - indexed for MEDLINE]
Ann Neurol. 2001 May;49(5):636-42. Related Articles, Links
Cellular and humoral immune response in progressive multifocal leukoencephalopathy.
Weber F, Goldmann C, Kramer M, Kaup FJ, Pickhardt M, Young P, Petry H, Weber T, Luke W.
Department of Neurology, University of Gottingen, Germany. firstname.lastname@example.org
Progressive multifocal leukoencephalopathy (PML) is a fatal, demyelinating disease caused by JC virus (JCV) in patients with severe immunosuppression. We studied the JCV-specific cellular and humoral immune response in 7 healthy donors (HD), 6 human immunodeficiency virus-1 (HIV-1)-infected patients without PML (HIV), 4 HIV-1-negative patients with PML (PML), and 8 HIV-1-positive patients with PML (HIV/PML).
As antigens, recombinant virus-like particles of the major structural protein VP1 (VP1-VLP) of JCV, tetanus toxoid (TT), or the mitogen phytohemagglutinin (PHA) were used. Proliferation of peripheral blood mononuclear cells (PBMC) after stimulation with the VP1-VLP was significantly suppressed in PML and HIV/PML patients compared to HD. After antigen stimulation the production of interferon-gamma (IFN-gamma) was reduced in PML, in HIV/PML, and in HIV patients.
The production of interleukin-10 (IL-10), however, was elevated in HIV/PML patients. Neither proliferation nor cytokine production correlated with the presence of JCV DNA in PBMC. The immunoglobulin G serum antibody titer to the VP1-VLP was slightly elevated in HIV, elevated in PML, and highly elevated in HIV/PML patients compared to HD. The development of PML appears to coincide with a general impairment of the Th1-type T-helper cell function of cell-mediated immunity.