Drug – bio-affecting and body treating compositions – Lymphokine
Patent
1991-07-17
1993-01-12
Cashion, Jr., Merrell C.
Drug, bio-affecting and body treating compositions
Lymphokine
A61K 3702
Patent
active
051788551
DESCRIPTION:
BRIEF SUMMARY
This invention relates to the treatment of leukocyte dysfunction associated with physical trauma, particularly thermal injury, by administering effective doses of GM-CSF.
GM-CSF is a lymphokine (stimulator of the immune system) that exhibits a broad spectrum of immune cell stimulation as described in Burgess and Metcalf, Blood, 56:947 (1980) and Metcalf, Blood 67:257 (1986). GM-CSF has been shown to increase the leukocyte count in patients with acquired immunodeficiency syndrome [Brandt et al., N. Engl. J. Med., 318:869 (1988)] and people suffering from chemotherapy-induced myelosuppression [Antman et al., New Engl. J. Med., 319:593 (1988), and it has been suggested that various colony stimulating factors alone or in combination with erythropoietin and/or an antiviral agent and/or interleukin-2 (IL-2) may be useful for the treatment of patients suffering form AIDS-type disease (PCT Application No. 87/03204).
Although GM-CSF was identified because of its ability to stimulate proliferation of hematopoietic precursor cells, it is also able to stimulate a number of functional aspects of mature granulocytes and macrophages. These effects include synthesis of biologically active molecules such as prostaglandin E [Hancock et al., J. Immunol., 140:3021 (1988) and Kurland et al., Proc. Natl. Acad. Sci. USA, 76:2326 (1979)]; increased phagacytic activity [Weisbart et al., Nature, 332:647 (1988)]; expression and/or affinity of various membrane markers such as the IL-2 receptor [Hancock et al., J. Immunol., 140:3021 (1988)] and the bacterial product formylmethionylleucylphenylalanine receptor on neutrophils, which receptors elicit the production of superoxide anions [Atkinson et al., Immunology, 64:519 (1988)]; and the regulation of enzyme activity such as the stimulation of guanylate cyclase and the inhibition of adenylate cyclase [Coffey et al., J. Immunol., 140:2695 (1988)].
In cases of physical trauma, such as thermal injury, there is an associated dysfunction of the white blood cells (WBC), particularly monocytes and leukocytes. Thus, although there may be sufficient numbers of WBC to function--i.e., engage in phagocytosis and superoxide generation--if operating normally, because of the leukocyte dysfunction there if a malfunction or suppression of the immune system. The immune system malfunction is attributable to the leukocyte dysfunction rather than to there being an insufficient number of leukocytes.
Those skilled in the art will appreciate that such leukocyte dysfunction jeopordizes the recovery of the physical trauma patient. For example, in the thermal burn patient such dysfunction can result in a greater risk of infection. To date no significant impact has been made in treating leukocyte dysfunction in vivo in thermal injury (burn) patients and the associated clinical consequences such as infection.
A welcome contribution to the art would be a method of treating leukocyte dysfunction associated with physical trauma, particularly thermal injury. Such a contribution is provided by this invention.
The invention may be summarized in the following manner. It has surprisingly and unexpectedly been discovered that leukocyte dysfunction associated with physical trauma, particularly thermal injury, can effectively be treated by the administration of GM-CSF. It has been discovered that GM-CSF administered to thermal injury patients results in increased leukocyte function--i.e., there is a potentiation of leukocyte function. Such treatment therefore result sin a significantly higher response to infection in thermal injury patients. The potentiation in vivo of leukocyte function with GM-CSF is to be distinguished from merely increasing the umber of dysfunctioning leukocytes. Since leukocyte dysfunction is also present in other types of physical trauma besides thermal injury, it is contemplated that leukocyte dysfunction associated with these other types of physical trauma are likewise treatable with GM-CSF.
Thus, in one embodiment this invention provides a method of treating leukocyte dysfunction in mammals, includin
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Cashion Jr. Merrell C.
Dulak Norman C.
Koh Choon
Lunn Paul G.
Nelson James R.
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