Modulation of cytokine and cytokine receptor/antagonist by treatment with doxycycline and tetracycline in patients with dengue fever.

Dengue virus infection can lead to dengue fever (DF) or dengue hemorrhagic fever (DHF). Disease severity has been linked to an increase in various cytokine levels. In this study, we evaluated the effectiveness of doxycycline and tetracycline to modulate serum levels of IL-6, IL-1B, and TNF and cytokine receptor/receptor antagonist TNF-R1 and IL-1RA in patients with DF or DHF. Hospitalized patients were randomized to receive standard supportive care or supportive care combined with doxycycline or tetracycline therapy. Serum cytokine and cytokine receptor/antagonist levels were determined at the onset of therapy and after 3 and 7 days. Cytokine and cytokine receptor/antagonist levels were substantially elevated at day 0. IL-6, IL-1ß, and TNF remained at or above day 0 levels throughout the study period in untreated patients. Treatment with tetracycline or doxycycline resulted in a significant decline in cytokine levels. Similarly, IL-1RA and TNF-R1 serum concentrations were elevated at baseline and showed a moderate increase among untreated patients. Both drugs resulted in a significant rise in IL-1Ra levels by day 3 in patients. In contrast, treatment did not affect a similar result for TNF-R1. When compared to the control group, however, a significant rise post-treatment was seen upon intragroup analysis. Further analysis demonstrated that doxycycline was significantly more effective at modulating cytokine and cytokine receptor/antagonist levels than tetracycline.

Protective effect of exogenous recombinant mouse interferon-gamma and tumour necrosis factor-alpha on ectromelia virus infection in susceptible BALB/c mice.

The resistance to mousepox is correlated with the production of type I cytokines: interleukin (IL)-2, IL-12, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha. We intend to describe the modulation of generalized ectromelia virus (EV) infection with exogenous administration of mrIFN-gamma and mrTNF-alpha separately and in combination using susceptible BALB/c mice. The treatment schemes presented resulted in the localization of the generalized EV infection and its development into non-fatal sloughing of the infected limb. This was accompanied by low virus titres in the treated mice due to control of systemic virus replication and virus clearance. The balance of type I versus type II cytokines was dominated by a type I response in the treated groups. The group treated with the combination of IFN-gamma and TNF-alpha exhibited the best survival with Th1-dominant (IFN-gamma and IL-12) cytokine profiles, whereas the TNF-alpha-treated group of mice was less successful in clearance of virus and demonstrated the lowest survival rate. The successful cytokine treatment schemes in this orthopoxvirus model system may have important implications in the treatment of viral diseases in humans and, in particular, of variola virus infection.

Changes in immune parameters and their correction in human cases of tick-borne encephalitis.

Tick-Borne Encephalitis virus (TBEV) causes dangerous central nervous system diseases in humans. General infection leads to the development of meningitis or encephalitis, which is characterized by swelling of the brain due to inflammation. Tetracyclines may act locally to moderate inflammation in the CNS. In this study, we investigated the potential clinical benefits of administering tetracycline hydrochloride to patients hospitalized due to suspected TBEV infection presenting with fever and evidence of a recent tick bite. We also characterized an acute immune response to TBEV by profiling certain cytokines and soluble receptors in Tetracycline-treated and untreated patients. Increased serum levels of TNF-alpha, IL-1 alpha and IL-6 were found in all patients at admission. Soluble receptors presented in the serum of patients in a magnitude higher levels than the corresponding cytokines and were increasing during first weak of hospitalization. Levels of IL-10 were also rising during that period. In our study tetracycline hydrochloride acted as an immunomodulator, which was able to reduce manifestations of inflammation response during TBE course; this action led to quicker improvement of symptoms and, consequently, to a faster clinical recovery. The positive result of tetracycline hydrochloride treatment was accompanied by certain particularities in the dynamics of studied cytokines and receptors: the concentrations of IL-6, IL-1 beta, TNF-alpha dropped quicker and reached lower levels, and the concentrations of sIL-6R, IL-1RA, sTNFR1 increased faster and reached higher maximum levels in the tetracycline-treated groups. Children had the highest levels of IL-6, which were not neurotoxic.

Simian foamy virus infection among zoo keepers.

We investigated 322 North American zoo workers in an anonymous serosurvey for antibodies to simian foamy viruses to establish the potential risk of zoonotic transmission by these retroviruses. 4 of 133 (3%) individuals who worked specifically with mammals including primates were seropositive, primarily with chimp-like viruses, indicating the importance of work practices to reduce exposure to these agents.

Comparison of the inflammatory responses of mice infected with American and Australian Trichinella pseudospiralis or Trichinella spiralis.

This study was designed to determine if the Tasmanian devil isolate of Trichinella pseudospiralis suppressed inflammation as does the original isolate. While adult worm numbers were similar in all groups, lower enteritis occurred in devil isolate-infected mice compared with mice infected with the original isolate of T. pseudospiralis or with Trichinella spiralis. Diaphragm muscle inflammation was greater in T. spiralis-infected than in mice infected with either isolate of T. pseudospiralis or concurrently infected with T. spiralis and either of the isolates of T. pseudospiralis. Granuloma inflammation was lower in mice infected with either isolate of T. pseudospiralis compared with uninfected or T. spiralis-infected mice. The devil isolate down-regulated inflammation more profoundly during the intestinal phase than the muscle phase compared to the original isolate, differences which may be related to the biology of their natural hosts.

Safety and immunogenicity of a polyvalent Escherichia coli vaccine in human volunteers.

Since a limited number of O serogroups account for nearly 70% of bacteremic and meningitic Escherichia coli isolates, a polyvalent vaccine was made by conjugating a Pseudomonas aeruginosa exotoxin A carrier protein to the O polysaccharide of 12 serogroups of E. coli (O1, O2, O4, O6-O8, O12, O15, O16, O18, O25, O75). No serious reactions occurred in 88 vaccinees. Four-fold or greater increases in ELISA antibody levels over baseline were greatest (> 60% of vaccinees) for O1, O2, O6-O8 and O15; intermediate (approximately 50%) for O18 and O75, and poorest (> or = 45%) for O4, O12, O16, and O25. Responses with functionally active opsonophagocytic antibody generally paralleled ELISA antibody responses. With the availability of a safe, immunogenic E. coli vaccine, active and passive immunization strategies merit further development as adjunctive treatment for E. coli bacteremia and neonatal meningitis.

Production and characterization of a human hyperimmune intravenous immunoglobulin against Pseudomonas aeruginosa and Klebsiella species.

A hyperimmune globulin for intravenous use (H-IVIG) was prepared from the plasma of donors immunized with Pseudomonas aeruginosa and Klebsiella vaccines. H-IVIG preparations contained substantially higher IgG antibody levels to all nine P. aeruginosa vaccine antigens and to 22 of the 24 Klebsiella vaccine antigens than did commercial IVIG. The H-IVIG was more effective at promoting the opsonophagocytic killing of P. aeruginosa and Klebsiella vaccine serotype strains than normal IVIG. The H-IVIG neutralized greater than 20 times more toxin A than commercial IVIG. Only the H-IVIG offered significant protection against Klebsiella K2 sepsis. The H-IVIG provided significantly better protection against six of the eight P. aeruginosa vaccine serotypes than normal IVIG when compared in a murine burn wound sepsis model. The H-IVIG also protected mice against an Enterobacter aerogenes challenge, whereas normal IVIG was ineffective.