[Antiviral and anti-stress activity of the gamma-L-glutamyl-histamine and its derivatives].
Effect of gamma-L-glutamylhistamine gamma-L-Glu-HA and some of its derivatives on the state of nonspecific resistance and antiviral activity was studied using experimental models of influenza virus and herpes simplex virus infections. Activities of natural killer (NK) cells and interferon (IFN) system were measured. The model of physical-emotional stress in mice was used. It was shown that the gamma-L-Glu-HA derivative II can prevent totally or substantially a decrease in the NK activity. This agent also prevents inhibition of synthesis of alpha- and gamma-IFN during the post-stress period. The gamma-L-Glu-HA derivatives II, III, and VII increased the mice resistance to influenza virus type A/Aichi at low infection dose (10LD50). The derivative II showed its protective effect even at high dose of pathogen (100LD50). However, this gamma-L-Glu-HA derivative was virtually ineffective under harsh experimental conditions. Thus, a number of gamma-L-Glu-HA derivatives tested in this work demonstrated immunomodulation activity. These agents were able to normalize parameters of nonspecific immunity. They exerted a pronounced antiviral effect against influenza virus but were virtually ineffective against encephalitis in mice caused by herpes simplex virus, type 1. Of all tested agents, gamma-L-Glu-HA derivative II was found to be the most promising.
Nosik
N N
NN
Nebol'sin
V E
VE
Zheltukhina
G A
GA
Evstigneeva
R P
RP
Kondrashina
N G
NG
Lavrukhina
L A
LA
Krzhechkovskaia
V V
VV
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006561:Herpes Simplex / Q000188:drug therapy* / Q000276:immunology; D018258:Herpesvirus 2, Human / Q000187:drug effects; D006632:Histamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D029521:Alphainfluenzavirus / Q000187:drug effects; D016898:Interferon-alpha / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D013312:Stress, Physiological / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors
D000276:Adjuvants, Immunologic; D014151:Anti-Anxiety Agents; D016898:Interferon-alpha; C013541:gamma-glutamylhistamine; D006632:Histamine; D007371:Interferon-gamma