The results demonstrate an association between EBV reactivation and disease activity in MS patients over time, and suggest that EBV might play an indirect role in MS as an activator of the underlying disease process.
Tumour necrosis factor (TNF) was first described as a factor in the serum of mice injected with tubercle bacilli (BCG) and several days later with lipopolysaccharide (LPS). The gene encoding TNF has recently been cloned and pure recombinant human TNF is now available. TNF is known for its in vivo antitumour effect and in vitro cytotoxicity on certain transformed cell lines. Similarities in amino acid sequence and biological activity to lymphotoxin and cachectin have been reported, and very recently a growth-factor-like activity on diploid fibroblasts was observed. There is no similarity between these proteins and interferons (IFNs), which are also induced during in vivo induction of TNF. Here we describe the antiviral activity of pure recombinant human TNF in a typical in vitro antiviral assay which we discovered while investigating the possible role of TNF as an inducer of IFN.
Although the intriguing role of zinc as an essential trace element for immune function is well established, particular progress in determining the molecular principles of action of this ion was made recently. Leukocyte responsiveness is delicately regulated by zinc concentration. Zinc deficiency as well as supraphysiologic levels impair immune function. Furthermore, the activities of many immunostimulants frequently used in immunologic studies are influenced by zinc concentration. Therefore, our knowledge from in vitro studies is widely dependent on the zinc concentration, and when not in physiologic range, immunologic responses are artificially low. Decreased production of TH1 cytokines and interferon-alpha by leukocytes in the healthy elderly person is correlated with low zinc serum level. The defect in interferon-alpha production is reconstituted by the addition of physiologic amounts of zinc in vitro. Interestingly, zinc induces cytokine production by isolated leukocytes. Zinc induces monocytes to produce interleukin-1, interleukin-6 and tumor necrosis factor-alpha in peripheral blood mononuclear cells and separated monocytes. This effect is higher in serum-free medium. However, only in the presence of serum does zinc also induce T cells to produce lymphokines. This effect on T cells is mediated by cytokines produced by monocytes. Stimulation also requires cell-to-cell contact of monocytes and T cells. Information is presented to illustrate the concepts that the zinc concentration must be taken into account whenever in vitro studies are made or complex alterations of immune functions are observed in vivo.
We have carried out a longitudinal study of interferon (IFN) and tumor necrosis factor (TNF) using a whole-blood mitogen stimulation assay in 20 multiple sclerosis (MS) patients and in a healthy control group. We set up individual profiles and the results were quite constant for each individual, both in healthy donors and in the patients in remission. Before exacerbations, however, we found an increase of IFN-gamma and TNF production preceding clinical symptoms by a maximum of 2 weeks. In benign cases, the increase disappeared rapidly, even before the appearance of symptoms, whereas we found sequelae whenever the increase persisted during weeks. In chronic progressive patients, we frequently found intervening increases. It may be that IFN-gamma and TNF trigger off exacerbations at a very early stage and that these cytokines may also play a role in maintaining disease in chronic progressive and invalidating forms.
Although human papillomavirus (HPV), a sexually transmitted virus, is established as a necessary cause for more than 95% of cervical carcinomas, the association with oral squamous cell carcinoma is less well delineated. The purpose of this study was to determine the frequency and types of HPV in squamous cells of a group of patients with newly diagnosed oral or pharyngeal cancer (n = 93) compared with an age- and gender-frequency-matched control group of patients with no history of oral cancer (n = 205). HPV was evaluated from a mouth rinse collection of cells in the oral cavity and tested by 32P-labeled HPV generic probes and DNA sequencing for HPV types. HPV was identified in 15% of the oral cancer cases but in fewer than 5% of the controls (P < .05). The risk of cancer associated with HPV infection was independent of tobacco and alcohol use (adjusted odds ratio [OR] = 3.70; 95% confidence interval [CI]: 1.47-9.32; P < .05). HPV types included similar and other types not identified previously in the genital tract. There was no statistically significant increased risk of cancer among former tobacco users (former vs. never users: adjusted OR = 0.67, 95% CI: 0.31-1.44, P < .05), but the risk was significantly increased for current users (current vs. never: adjusted OR = 2.63; 95% CI: 1.22-5.71; P < .05). Likewise, former alcohol users were not at increased risk of disease (former vs. never: adjusted OR = 1.78; 95% CI: 0.87-3.67), whereas current alcohol users were (current vs. never: adjusted OR = 2.57; 95% CI: 1.22-5.42; P < .05). HPV-related genital lesions (14.3% vs. 10.6%), oral-genital sexual behavior (42.4% vs. 45.2%), and number (11 or more) of sexual partners (23% v. 17%) were not significantly different between cases and controls. These data suggest that in addition to tobacco and alcohol, HPV plays a role in the development of oral cancer.
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