Effect of muramyl dipeptide and its stearoyl derivatives on resistance to Sendai virus infection in mice

The efficacy of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), 6-O-stearoyl-MDP (L18-MDP), N alpha-acetylmuramyl-L-alanyl-D-isoglutaminyl-N epsilon-stearoyl-L-lysine (MDP-Lys-L18) and N-stearoylmuramyl-L-alanyl-D-isoglutamine (2N-L18-MDP) for augmenting host-resistance to viral infection was examined in Sendai virus infected mice. L18-MDP and MDP-Lys-L18 augmented the non-specific host-resistance to infection with Sendai virus. MDP showed a slight enhancement of host-resistance to this infection but 2N-L18-MDP was ineffective. The protective effect of MDP-Lys-L18 was seen only when the drug was administered a few days before the virus challenge. The intranasal administration of MDP-Lys-L18 was effective at 1 microgram but only slight activity was observed in mice treated intravenously or intraperitoneally even at the 100 microgram dose level. MDP-Lys-L18 treatment preceding infection augmented interferon production in the lung of the mice but MDP-Lys-L18 treatment alone induced no interferon.     

Prophylactic activity of dihydroheptaprenol, a synthetic polyprenol derivative, against Sendai virus infection in mice.

The effect of a chemically synthesized polyprenol derivative, dihydroheptaprenol (DHP), on the non-specific resistance of mice to Sendai virus infection was investigated. The mice that received 200 micrograms of DHP intranasally twice, at 3 days and 1 day before the infection, showed a significant protection against Sendai virus infection. Treatment of mice twice even with as much as 2000 micrograms of DHP through the subcutaneous route, however, had no protective effect against infection. Excess interferon and tumour necrosis factor production in intranasally DHP-treated mice was seen 1 day after the infection when compared with Sendai virus alone controls or with DHP alone controls. Variance analysis of these findings indicates a prophylactic activity of DHP in pulmonary viral infections.     

Stimulation of non-specific host resistance against Sendai virus and Escherichia coli infections by chitin derivatives in mice

The efficacy of chitin derivatives on non-specific host resistance to Sendai virus and Escherichia coli infections was studied in mice. Seventy percent deacetylated chitin (DAC-70) and N-trimethylated DAC-70 [DAC-70(Me)₃] showed protective activity against Sendai virus infection; however, carboxymethyl-chitin (CM-chitin) did not. DAC-70 also showed protective activity against E. coli infection.     

Suppression of Sendai virus growth by treatment with N alpha-acetylmuramyl-L-alanyl-D-isoglutaminyl-N epsilon-stearoyl-L-lysine in mice

Mice that received N alpha-acetylmuramyl-L-alanyl-D-isoglutaminyl-N epsilon-stearoyl-L-lysine [MDP-Lys (L18)] were resistant to Sendai virus infection. In these protected mice, a significant growth inhibition of the virus was confirmed repeatedly at 10(0.2) to 10(0.4) of haemadsorbing units at an early non-specific phase but not at a late virus-eliminating phase of the infection. Virus growth was enhanced by treatment with silica but not by treatment with anti-asialo GM1 serum in MDP-Lys (L18)-treated mice. Peritoneal adherent cells activated by MDP-Lys(L18) showed an enhanced uptake and ability to inactivate Sendai virus in vitro. Excess interferon production in MDP-Lys (L18)-treated mice was seen on day 1 but not on days 2 to 7 of the infection. The possible role of macrophages and interferon in providing non-specific protection against Sendai virus in the MDP-Lys (L18)-treated mice is discussed.     

Effect of N alpha-acetylmuramyl-L-alanyl-D-isoglutaminyl-N epsilon-stearoyl- L-lysine on resistance to herpes simplex virus type-1 infection in cyclophosphamide-treated mice

The restoration of resistance by N alpha-acetylmuramyl-L-alanyl-D-isoglutaminyl-N epsilon-stearoyl-L-lysine [MDP-Lys(L18)] on herpes simplex virus (HSV) type-1 infection was examined in cyclophosphamide (CY)-treated mice. MDP-Lys(L18) was shown to restore the resistance to HSV infection in CY-treated mice when it was injected either subcutaneously, intravenously, or intraperitoneally before infection. Treatment with MDP-Lys(L18) in CY-treated mice restored impaired activity for inhibiting HSV growth in the liver.     

Effects of sulfur dioxide on resistance to bacterial infection in mice

Continuous exposure to approximately a 10-ppm concentration of sulfur dioxide for periods of up to 3 weeks reduced the resistance of female mice to infection by aerosol inoculation with Klebsiella pneumoniae. The mortality rate rose and survival time shortened in SO₂-exposed animals compared to controls. Insofar as these results can be extrapolated to humans, the SO₂ concentration used in this work is only found on certain industrial premises.     

Lactobacillus casei improves resistance to pneumococcal respiratory infection in malnourished mice

We studied the effect of Lactobacillus casei CRL 431 used as a supplement in a repletion diet on the resistance to Streptococcus pneumoniae respiratory infection in malnourished mice. Weaned mice were malnourished after they consumed a protein-free diet (PFD) for 21 d. Malnourished mice were fed a balanced conventional diet (BCD) with or without supplemental L. casei for 7, 14, or 21 consecutive days, or BCD for 7 d with L. casei supplementation on d 6 and 7 (7dBCD+2dLc). The malnourished control (MNC) group was fed only the PFD, whereas well-nourished control (WNC) mice consumed the BCD ad libitum. Mice were challenged with S. pneumoniae at the end of each dietary treatment. Lung colonization and bacteremia were significantly greater in MNC than in WNC. Normalization of the immune response occurred in malnourished mice fed the BCD for 21 d. L. casei supplementation reduced the time required for a normal response from 21 to 7 d. Mice administered the 7dBCD+2dLc repletion treatment had a more effective pathogen clearance from blood and significantly lower lung damage than MNC. This treatment improved both the number of leukocytes and neutrophils in blood and bronchoalveolar lavages (BAL) and the bactericidal function of phagocytic cells to levels that did not differ from those of WNC. In the 7dBCD+2dLc mice, antipneumococcal IgA in BAL was higher than in WNC, whereas antipneumococcal IgG in serum and BAL did not differ. This study suggests that the addition of L. casei to the repletion diet has a beneficial effect because it accelerates the recovery of the innate immune response and improves the specific immune mechanisms against an S. pneumoniae respiratory infection in malnourished mice.     

Protective activity of recombinant cytokines against Sendai virus and herpes simplex virus (HSV) infections in mice

The efficacy of recombinant cytokines such as murine interferon-gamma (IFN-gamma), human granulocyte colony-stimulating factor (G-CSF), mouse granulocytic-macrophage colony-stimulating factor (GM-CSF) and human interleukin-1 beta (IL-1 beta) has been examined for augmentation of host resistance against Sendai virus and herpes simplex virus (HSV) infections. All four cytokines were found to protect mice against Sendai virus infection. IFN-gamma afforded protection when administered intranasally but not intravenously several days before the infection. Intranasal administration of G-CSF one day before the infection was the most effective administration route and timing. Intranasal administration of GM-CSF was found to afford protection 1 or 3 days before the infection. IL-1 beta demonstrated therapeutic activity against Sendai virus infection after intranasal administration on the same day as the infection. When each of the cytokines was administered subcutaneously four times daily into cyclophosphamide-treated mice before intravenous infection with HSV, only GM-CSF revealed any protective activity.     

Phagocytosis and resistance to Salmonella typhimurium infection in mice fed with lipidic diet

The peritoneal macrophages from mice on a lipidic diet have shown an increase of surface hydrophobicity of cytoplasmatic membrane. This fact is correlated with a decrease of the phagocytic index and with an impairment of Salmonella typhimurium.[/p]Corresponding author.     

Effect of timing of food deprivation on host resistance to fungal infection in mice

Mice were deprived of food for a period of 72 h at varying times relative to the time of infection with Paracoccidioides brasiliensis. Host resistance was diminished profoundly when the period of food deprivation was from 48 h before to 24 h after infection (group B). When food deprivation was initiated immediately after infection (group C), host resistance was reduced less profoundly. When food deprivation was initiated at 24 and 48 h post-infection, reductions in host resistance were only moderate or not observed respectively. These results suggest that the earlier in the course of infection starvation occurs, the more profoundly host resistance is impaired. When food deprivation was initiated 72 h before infection, finishing at the time of infection (group A), the reduction in host resistance was considerably less profound compared with group B mice, suggesting that refeeding initiated immediately after infection is responsible for rapid restoration of the antifungal resistance in starved mice. Infection-induced responses of corticosterone and interferon-gamma were changed according to the timing of food deprivation. Group A mice, similar to non-fasted controls, showed an infection-induced increase in serum corticosterone concentration, while groups B and C did not. Group C mice showed a substantially greater infection-induced increase in serum interferon-gamma compared with the other fasted and non-fasted control groups.     

Influenza virus infection in mice after exposure to coal dust and diesel engine emissions

Influenza virus infection initiated after aerosol exposure of CD-1, white Swiss mice for durations of 1, 3, and 6 months to respirable particulates maintained at 2 mg/m3 of either coal dust (CD), diesel engine emissions (DEE), a combination of both (CD/DEE), or to filtered air (control) was studied. The course of infection in mice previously exposed for 1 month to various particulates did not differ appreciably among the four animal groups with respect to mortality, virus growth in lungs, interferon levels, or hemagglutinin antibody response. In mice exposed for 3 and 6 months to different particulates, the mortality response was similar among all animal groups. However, the percentage of animals showing lung consolidation was significantly higher in the 3-month groups exposed to DEE (96.5%) and CD/DEE (97%) than in the control (61.2%); in the 6-month groups, the percentages were twice that of the control for both DEE- and CD/DEE-exposed animals. Complementing these observations of both 3- and 6-month-exposed animals was the higher virus growth levels attained in the DEE and CD/DEE animals with concomitant depressed interferon levels which were the inverse of findings noted in the control group. Hemagglutinin-antibody levels in particulate-exposed animals, especially at the 6-month interval, were fourfold less than the control. Histopathologic examination of lungs revealed no qualitative differences in the inflammatory response at any one specified time interval of exposure to influenza virus among the control and particulate-exposed animal groups. However, there were differences in severity of reaction in relation to the particulate component of the exposures. Focal macular collections of pigment-laden macrophages were seen only in DEE and CD/DEE but not in CD animals after 3- and 6-month exposures. The findings of this study indicated that the severity of influenza virus infection is more pronounced in mice exposed to diesel engine emissions than in control animals and it is not appreciably accentuated by coal dust.     

Clinicopathologic understanding and control of varicella-zoster virus infection

As reflections by the recipient for the Japanese society for vaccinology Takahashi award, clinicopathologic understanding and control of varicella-zoster virus (VZV) infection was briefly reviewed. In 1974, a live varicella vaccine was developed by attenuating the Oka strain of VZV after the passages in non-human cells at a low temperature. The vaccine was immunogenic, well tolerated, and effective, and distributed worldwide so far. For post-exposure prophylaxis of varicella, the vaccine and acyclovir is effectively used in the incubation period of varicella. The delayed type hypersensitivity to VZV skin test antigen was applied for evaluation of cell-mediated immunity to VZV which is commercially available in Japan. The biphasic viremia during incubation period of varicella and airborne spread of VZV from varicella patients and from herpes zoster patients with localized lesions were shown by the virus isolation or by detection of the virus DNA.     

Prophylactic activity against Sendai virus infection and macrophage activation with lipophilic derivatives of N-acetylglucosaminylmuramyl tri- or tetrapeptides

The efficacy of N-acetylglucosaminyl-beta (1----4)-N-acetylmuramyl tri- or tetrapeptides (GM) and the lipophilic derivatives for host augmentation against Sendai virus infection and for macrophage activation in vitro was examined. The anti-infectious activities of GM derivatives were shown to increase with the chain length of the fatty acid combined with the diaminopimelyl group. When the macrophages were activated with 1 U ml-1 murine interferon gamma (IFN-gamma) and 0.001 microgram ml-1 GM derivatives, the cytocidal ability of macrophages depended on the length of the side chain, and exhibited a positive relationship with the anti-infectious activity of GM derivatives against Sendai virus infection. These results indicated that the increment of lipophilicity of GM derivatives would play an important role in the anti-infectious activity and macrophage activation in vitro.     

感染控制与抗菌药物管理齐头并进有效遏制细菌耐药

细菌耐药(A MR)已经成为全球公共卫生安全危机,世界卫生组织要求全球各国积极行动,采取系统性措施遏制细菌耐药.此文从耐药细菌发生过程、危险因素和控制策略等方面进行阐述,表明A MR的发生和传播与抗菌药物使用、感染控制息息相关,提示控制A MR必须同时开展抗菌药物临床应用管理和感染控制,两者相互协同才能取得成功.