Protein calorie malnutrition (PCM) is the most common cause of secondary immunodeficiency worldwide and in hospitalized patients substantially increases infection and mortality. The frequent presence of associated disease such as infection and malignancy often obscures underlying basic immune abnormalities. Therefore, controlled laboratory investigations are necessary to understand immune dysfunction and plan therapeutic interventions. The macrophage (MO) plays a critical role in humoral and cell-mediated immunity. Phagocytic and microbicidal activity, antigen presentation, and cytokine release are central to the role of this cell in the orchestration of the immune response. Preliminary work from our laboratory shows that PCM significantly alters Mo function which leads to significant adverse consequences to the host. Specific projects in this proposal aim to identify the effects of PCM on MO antimicrobial mechanisms [release of toxic oxygen and nitrogen metabolites] and cytokine release [TNF, IL-1, and IL-6] as well as antigen presentation. Defects in cell surface receptor expression [mannose, Fc receptor] and signal transduction pathways [membrane phospholipids, cytosolic Ca++, and protein kinase C] will be studied. The potential of g-Interferon and IL-4 to upregulate macrophage function will be assessed in an attempt to identify cytokine approaches to therapeutic intervention in the malnourished host. Global prevalence of protein calorie malnutrition [PCM] demands a clear understanding of the specific immunologic defects induced by this nutritional state. Elucidation of these effects should be of benefit both in the understanding of PCM-induced immunodeficiency and in the development of therapeutic regimens in the malnourished host.
