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Stimulation of host resistance to infection
226
Passive protection against Ps. aeruginosa A commercially available human IgG preparation suitable for i.v. use was found to have a protective effect on burned mice infected with any one of 5 different immunotypes of Ps. aeruginosa but not against 2 other immunotypes of the same organism. With the sensitive strains of pseudomonas the IgG preparation reduced the 15 day mortality from 84 per cent in untreated animals to less than 30 per cent. The protective effect could be induced by giving the IgG preparation at any time up to 12 hours after the infective challenge. Collins M. S. and Roby R. E. (1983) AntiPseudomonas aeruginosa activity of an intravenous human IgG preparation in burned mice. .I. Trauma 23,530.
Complement activation in burned mice There was massive activation of the alternative complement pathway but not the classical pathway in mice with full-thickness skin loss bums covering 25 per cent of the body surface area. The activation-was asssociated with the generation of neutrophil aggregating activity in the plasma, neutrophil aggregates in the lungs, increased pulmonary vascular permeability and increased formation of lung oedema. Preventing complement activity with cobra venom or a genetic deficiency of Cs diminished these pathological changes and substanttally reduced bum mortality in the first 24 hours after burning. Gelfand J. A., Donelan M., Hawiger A. et al. (1982) Alternative complement pathway activation increases mortality in a model of bum injury in mice. J. Clin. Invest. 70, 1170. Stimulation of host resistance to infection Guinea-pigs with deep scalds covering 20 per cent of the body surface are highly susceptible to a challenge with virulent strains of Ps. aeruginosa within 24 hou@ of injury and the susceptibility persists for about 7 days. This model has been used to test the ability of 6 synthetic immuno-modulators to stimulate the impaired host resistance to infection induced by buming injury. Four of the synthetic immuno-modulators had no beneficial effect. Compounds CP 46665 and TP5 increased the survival rates from 50 to 85 per cent and 40 to 80 per cent respectively and the mean survival times from 8.2 to 12.4 days and from 6.9 to 1 I .6 davs respectively. Thus some svnthetic immunomodulators improve host resistance to infection with Ps. aeruginosa.
Burns
Vol. 1 O/No.
3
Stinnett J. D., Loose L. D., Miskell P. et al. (1983) Synthetic immunomodulators for prevention of fatal infections in a burned guinea pig model. Ann. Surg. 198, 53.
Metabolic changes in burned rats Rats with bums covering 25 per cent of the body surface were given a 15 g diet per day and were maintained at environmental temperatures of 20°C or 30 “C. At 20°C the rats showed a negative energy balance and they lost weight. The major component of the weight loss was fat. Much of the increased energy production was associated with the latent heat of evaporation of water from the burned tissue. At 30 “C evaporative heat loss was still high but the radiative losses were much lower than at 20°C leading to a positive energy balance and gains in body weight and lower urine levels of catecholamines, nitrogen and 3 methyl histidine. However as these urine constituents were still abnormally high at 30°C part of the metabolic response to burning injury appears to be obligatory. Gedeon G. S., Go11 C., Shenkin A. et al. (I 983) The effect of environmental temperature on protein and energy changes following bum injury in the rat. Clin. Nutr. 2, 13.
Acquisition of resistance to burning Rat paws scalded on two occasions, the second occurring 72 hours aRer the first, showed the acquisition of local-but not systemic-resistance to the subsequent scald with minimal inflammation and oedema following the second scald. The administration of chlorpromazine 30 minutes before a single scald also minimized the formation of inflammation and oedema. The inflammatory and tissue oedema responses induced by heat have been considered to arise from a combination of the effects of neurogenic stimuli, histamine, serotonin, bradykinin and products from prostaglandin stimulation of mast cells. Chlorpromazine has gangliolytic, adrenolytic, antiserotonin and antihistamine properties and has, therefore, been used in this study to explore the mechanisms involved in the acquisition of resistance to scalding. Bibi R. R., Babyatsky M. and Levenson S. M. (1983) Acquired local resistance to bums: prevention of its acquisition by chlorpromazine. Burns 9, 387.
Passive protection against Ps. aeruginosa A commercially available human IgG preparation suitable for i.v. use was found to have a protective effect on burned mice infected with any one of 5 different immunotypes of Ps. aeruginosa but not against 2 other immunotypes of the same organism. With the sensitive strains of pseudomonas the IgG preparation reduced the 15 day mortality from 84 per cent in untreated animals to less than 30 per cent. The protective effect could be induced by giving the IgG preparation at any time up to 12 hours after the infective challenge. Collins M. S. and Roby R. E. (1983) AntiPseudomonas aeruginosa activity of an intravenous human IgG preparation in burned mice. .I. Trauma 23,530.
Complement activation in burned mice There was massive activation of the alternative complement pathway but not the classical pathway in mice with full-thickness skin loss bums covering 25 per cent of the body surface area. The activation-was asssociated with the generation of neutrophil aggregating activity in the plasma, neutrophil aggregates in the lungs, increased pulmonary vascular permeability and increased formation of lung oedema. Preventing complement activity with cobra venom or a genetic deficiency of Cs diminished these pathological changes and substanttally reduced bum mortality in the first 24 hours after burning. Gelfand J. A., Donelan M., Hawiger A. et al. (1982) Alternative complement pathway activation increases mortality in a model of bum injury in mice. J. Clin. Invest. 70, 1170. Stimulation of host resistance to infection Guinea-pigs with deep scalds covering 20 per cent of the body surface are highly susceptible to a challenge with virulent strains of Ps. aeruginosa within 24 hou@ of injury and the susceptibility persists for about 7 days. This model has been used to test the ability of 6 synthetic immuno-modulators to stimulate the impaired host resistance to infection induced by buming injury. Four of the synthetic immuno-modulators had no beneficial effect. Compounds CP 46665 and TP5 increased the survival rates from 50 to 85 per cent and 40 to 80 per cent respectively and the mean survival times from 8.2 to 12.4 days and from 6.9 to 1 I .6 davs respectively. Thus some svnthetic immunomodulators improve host resistance to infection with Ps. aeruginosa.
Burns
Vol. 1 O/No.
3
Stinnett J. D., Loose L. D., Miskell P. et al. (1983) Synthetic immunomodulators for prevention of fatal infections in a burned guinea pig model. Ann. Surg. 198, 53.
Metabolic changes in burned rats Rats with bums covering 25 per cent of the body surface were given a 15 g diet per day and were maintained at environmental temperatures of 20°C or 30 “C. At 20°C the rats showed a negative energy balance and they lost weight. The major component of the weight loss was fat. Much of the increased energy production was associated with the latent heat of evaporation of water from the burned tissue. At 30 “C evaporative heat loss was still high but the radiative losses were much lower than at 20°C leading to a positive energy balance and gains in body weight and lower urine levels of catecholamines, nitrogen and 3 methyl histidine. However as these urine constituents were still abnormally high at 30°C part of the metabolic response to burning injury appears to be obligatory. Gedeon G. S., Go11 C., Shenkin A. et al. (I 983) The effect of environmental temperature on protein and energy changes following bum injury in the rat. Clin. Nutr. 2, 13.
Acquisition of resistance to burning Rat paws scalded on two occasions, the second occurring 72 hours aRer the first, showed the acquisition of local-but not systemic-resistance to the subsequent scald with minimal inflammation and oedema following the second scald. The administration of chlorpromazine 30 minutes before a single scald also minimized the formation of inflammation and oedema. The inflammatory and tissue oedema responses induced by heat have been considered to arise from a combination of the effects of neurogenic stimuli, histamine, serotonin, bradykinin and products from prostaglandin stimulation of mast cells. Chlorpromazine has gangliolytic, adrenolytic, antiserotonin and antihistamine properties and has, therefore, been used in this study to explore the mechanisms involved in the acquisition of resistance to scalding. Bibi R. R., Babyatsky M. and Levenson S. M. (1983) Acquired local resistance to bums: prevention of its acquisition by chlorpromazine. Burns 9, 387.