Immunosuppression in rabies virus infection mediated by lymphocyte apoptosis.

Previously, we demonstrated a depression of cell-mediated immunity in mice by street rabies virus infection. In the present study, we investigated several events during the course of infection and looked for alterations in the host lymphoid cells for evidence of apoptosis. Total cellular RNA was extracted from muscle tissues at the inoculation site of peripherally infected mice at different intervals after infection. Rabies virus mRNA was monitored by reverse transcription-PCR. The length of virus localization at the site of exposure in the muscle was as long as 5 days post-inoculation before the virus entered the central nervous system. At this inoculation site, the virus disappeared transiently between days 7 and 9 after infection but then was restored thereafter until death. Annexin V-fluorescein isothiocyanate staining of splenocytes and thymocytes from mice revealed apoptotic changes in these cells with a marked increase after day 6 of infection. Rabies virus antigen in the brain became detectable 6 days after infection; this occurred parallel to the appearance of apoptosis in the lymphoid cells. There was atrophy of the spleen and thymus, with no evidence of infection. Our results suggest that the interaction between the rabies virus and infected neurons triggers the process of lymphoid cell apoptosis, which reflects the defective operation of the immune system.

Prevalence of CCR2-64I, SDF1-3'A and CCR5-Delta32 alleles in healthy Thais.

A genetic survey was performed of 200 healthy Thai blood donors for the frequency of three alleles that influence susceptibility to HIV infection and the rate of progression to HIV disease. The CCR5-Delta32 allele was not detected in this population. The CCR2-64I allele was detected at a frequency similar to that found in other Asian populations (15.7%). SDF1-3'A was detected at 33.2%, supporting a cline of increasing frequency of this allele from African and Caucasian to Asian (particularly Australasian) populations. These results have implications for the role of host genetic background in the biology and pathology of HIV in Thailand, and indicate that a systematic survey of non-Caucasian populations may reveal novel alleles important in HIV disease.

IL-1beta, IL-6 and TNF-alpha in synovial fluid of patients with non-gonococcal septic arthritis.

Interleukin-1 beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) are the main proinflammatory cytokines responsible for the inflammatory process and cartilage destruction of inflammatory arthropathies. The present study sequentially measured the concentrations of these cytokines and their proportions of detectable levels in the synovial fluid (SF) of 23 patients with non-gonococcal (GC) septic arthritis before and after treatment. Persistently high concentrations and proportions of IL-6 and TNF-alpha were found up to day 7 of treatment, while SF IL-1beta concentration declined significantly after day 7 (p = 0.036). SF IL-1beta and TNF-alpha correlated with each other significantly and with SF WBC counts (p < 0.01). Positive correlations between SF IL-1beta concentration and joint effusion (p < 0.01) and between SF TNF-alpha concentration and joint tenderness (p < 0.001) were observed. SF IL-1beta and TNF-alpha were significantly higher in patients with local complications of septic arthritis. In conclusion, high levels of IL-1beta, IL-6 and TNF-alpha were detected in SF of patients with non-GC septic arthritis. Only IL-1beta decreased significantly after day 7 of treatment, but IL-6 and TNF-alpha concentrations were persistently high. SF IL-1beta and TNF-alpha may be useful in predicting the outcome and complications of patients with this disease.

International clinical trials of HIV vaccines: I. Phase I trial of an HIV-1 synthetic peptide vaccine in Bangkok, Thailand.

A randomized, double blind, placebo controlled Phase I trial of a prototype human immunodeficiency virus type 1 (HIV-1) synthetic peptide vaccine was conducted in Bangkok, Thailand, to evaluate the safety and immunogenicity of the vaccine in a population of healthy adults at low risk for HIV infection, and to establish essential infrastructure for future HIV vaccine trials in Thailand. Thirty volunteers (25 males; 5 females) were recruited and randomized into 3 groups, receiving 3 intramuscular injections of either 100 micrograms vaccine (N = 12) or 500 micrograms vaccine (N = 12) or alum placebo (N = 6) on weeks 0, 4 and 25. The vaccine was well tolerated without any serious adverse effects. HIV-1 specific ELISA responses were detected in 20/24 subjects who received the vaccine, with V3 binding antibody titers ranging from 1:69 to 1:5,041. HIV-1 (MN) specific neutralizing antibody was detected in 19/20 of subjects with detectable HIV-1 specific binding antibody. Neutralization titers ranged from 1:14 to 1:1,294, which were less than titers observed in HIV-infected subjects. The results of this study indicate that the vaccine was well tolerated, and that the vaccine stimulated anti-HIV humoral immune responses in Thai subjects. The successful undertaking of this first HIV vaccine trial conducted in Thailand provided important preparatory information surrounding volunteer recruitment and motivations, and paves the way for future trials of HIV vaccines in Thailand.