The ultrastructural finding of viral particles identical to VZV, together with the simultaneous presence of large quantities of DNA from VZV in the subarachnoid space, almost restricted to the periods of exacerbation, as well as its steady diminution and eventual disappearance from clinical relapse to clinical remission are surprising and constitute the strongest evidence to support the participation of VZV in the pathogenesis of MS.

The possible participation of different herpes viruses was studied during exacerbations of multiple sclerosis (MS). We searched for the presence of DNA from the following herpes viruses: varicella zoster virus (VZV), herpes-simplex viruses 1 and 2; Epstein-Barr virus (EBV) and human herpes-virus-6 (HHV6) in mononuclear cells from patients with MS during relapse (n = 40), MS during remission (n = 131) and controls (n = 125). Additionally, immune cells containing viral antigens were quantified by flow cytometry, and VZV load was determined by real time PCR in 2 MS patients at various times during relapse and remission. DNA from VZV was found in 95% of MS patients during relapse and in 17% during remission; all controls were negative; by contrast, DNA from HHV6 was found in 24% of MS patients during relapse and in 2% during remission; DNA from herpes simplex viruses was not found in any subject; and DNA from EBV was found in a similar percentage of subjects from all groups. Sequential quantification of VZV-load showed a curve that increased during relapse and disappeared at remission. Also, VZV antigens were found inside a large number of immune cells from MS patients during relapse as compared with MS patients on remission and controls. In the typical forms of VZV infection, varicella and herpes-zoster, DNA from VZV is found in mononuclear cells exclusively during brief periods at the beginning of the active infection, but not during latency; thus, the conspicuous presence of VZV during relapses of MS may indicate a period of active infection and suggests the participation of VZV in the pathogenesis of MS.

The finding of genes of VZV in peripheral mononuclear cells, restricted to a brief period during clinical relapse of MS, suggests either its participation in the etiopathogenesis of MS or an epiphenomenon of viral activation simultaneous with the relapse of MS.

The purpose of this study is to determine immune recovery and function after treatment with docetaxel or paclitaxel. Peripheral blood mononuclear cells were harvested before chemotherapy and at weekly times afterwards for cycle 1. Leukocyte subsets ICD45hiCD14lo polymorphonuclear neutrophils, CD45hiCD14hi monocytes, CD45hiCD14- lymphocytes, CD3+CD4/CD8+ T cells, CD3-CD19+ B cells, CD3-CD16/CD56+ natural killer (NK) cells], and circulating cytokine levels [tumor necrosis factor-alpha, gamma-interferon (gamma-IFN), and interleukins (IL-2, IL-10, IL-12)] were followed. In addition, T-cell mitogenic function, NK function, and lymphokine activated killer (LAK) function was assessed. Ten patients were entered in the trial. T-cell frequency, B-cell frequency, and CD4/CD8 ratio did not change. IL-10 serum levels significantly decreased in paclitaxel-treated patients (4.4+/-1.3 pg/ml at week 4 versus 7.8+/-2.1 pg/ml at baseline; p < 0.05). IL-2, IL-12, and gamma-IFN levels were not detectable. NK cytotoxic activity decreased in docetaxel-treated patients. LAK cell activity was not altered. Four patients achieved a partial or complete response. They demonstrated higher than normal CD4:CD8 T-cell ratios and an improved phytohemagglutinin stimulation index (SI = 2.5). In conclusion, our findings suggest that immune function was affected more significantly after docetaxel treatment. Investigational approaches, which enhance cellular immunity, may be of greater relevance after treatment with docetaxel. Additional studies monitoring NK function after chemotherapy are recommended.