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Biologic response modifier OK-432 pretreatment reduces mortality in burned mice infected with gram-negative bacteria
I A Holder1, R G Miller, A N Neely
1Shriners Burns Institute, Department of Physiology, Cincinnati, Ohio 45229.
Abstract:
When compared with a control group, mice pretreated with the biologic response modifier OK-432 showed increased survival when burned and infected with several strains of Pseudomonas aeruginosa and a Klebsiella pneumoniae isolate. Quantitative microbial counts in the skin, liver, and kidneys of burned mice infected with Pseudomonas aeruginosa showed that although skin counts were not different between control groups pretreated or untreated with OK-432, liver and kidney counts were reduced significantly in the group pretreated with OK-432. We speculate from these results that OK-432 pretreatment may enhance survival by enhancing host clearance of microorganisms entering the circulation from the burn wound. Making mice granulocytopenic by cyclophosphamide treatment or macrophage-deficient/dysfunctional by carrageenan treatment nullified any survival advantage given by OK-432 pretreatment. These results supported our speculation and suggested that both of these cell types were important in the mechanisms of enhanced survival afforded by OK-432 pretreatment.
Insights
Biologic response modifier OK-432 increased survival in burned mice infected with bacteria. OK-432 enhanced host clearance of bacteria, with granulocytes and macrophages being crucial for this effect.
Area of Science:
- Immunology
- Microbiology
- Surgical Infection
Background:
- Burn wounds are susceptible to bacterial infections, leading to high mortality.
- Biologic response modifiers are being investigated to enhance host defense against infections.
Purpose of the Study:
- To investigate the effect of OK-432 pretreatment on survival and bacterial clearance in burned mice.
- To elucidate the role of host immune cells in OK-432-mediated protection.
Main Methods:
- Mice were pretreated with OK-432 or vehicle control before thermal injury and bacterial challenge (Pseudomonas aeruginosa, Klebsiella pneumoniae).
- Survival rates and quantitative microbial counts in skin, liver, and kidneys were assessed.
- Immune cell depletion models (cyclophosphamide for granulocytes, carrageenan for macrophages) were used to determine the role of specific cell types.
Main Results:
- OK-432 pretreatment significantly increased survival in burned, infected mice.
- Bacterial counts in the liver and kidneys were significantly reduced in OK-432-treated mice.
- The survival benefit of OK-432 was abolished in granulocytopenic or macrophage-deficient mice.
Conclusions:
- OK-432 enhances survival in burned mice challenged with Gram-negative bacteria.
- The protective effect of OK-432 is mediated by enhanced host clearance of bacteria from internal organs.
- Granulocytes and macrophages play a critical role in the mechanism of OK-432-induced enhanced survival.