A good understanding has also been developed the genesis of potentially harmful immunological responses to infection, such as those produced by immune complexes, autoimmunity, or allergy, or by the impairment of a key subset of lymphocytes, as seen in AIDS virus infections. The acute phase response during generalized infectious diseases includes many metabolic and physiological reactions. Activated monocytes, macrophages, and other body cells produce and release interleukin 1, which serves in a hormonelike role to trigger acute phase responses throughout the body. Although infectious diseases generally stimulate an immune response, an adverse secondary effect on the immune system and other host defense mechanisms may be created by the large nutritional costs of infection. A number of different hematological growth factors, termed colony-stimulating-factors, act in concert with interleukin 2 and interleukin 3 to enhance a full spectrum of red and white blood cells.

Malnutrition can have adverse, even devastating effects on the antigen-specific arms of the immune system and on generalized host defensive mechanisms. Protein/energy malnutrition and/or deficiencies of single nutrients that assist in nucleic acid metabolism generally lead to atrophy of lymphoid tissues and dysfunctions of cell-mediated immunity. Deficiencies of single nutrients can impair production of key proteins. Trace element deficiencies are often multifactorial. Essential fatty acid deficiencies can reduce or perturb the synthesis of cytokine-induced eicosanoids. Arginine deficiency can diminish the production of nitric oxide, and deficiencies of antioxidant nutrients can allow increases in the damaging effects of free oxygen radicals. Humoral immunity continues to be maintained, although new primary responses to T-cell-dependent antigens are generally subnormal in both magnitude and quality. Immunological dysfunctions associated with malnutrition have been termed Nutritionally Acquired Immune Deficiency Syndromes (NAIDS). Infants and small children are at great risk because they possess only immature, inexperienced immune systems and very small protein reserves. The combination of NAIDS and common childhood infections is the leading cause of human mortality. NAIDS can generally be corrected by appropriate nutritional rehabilitation, but from a viewpoint highly important to this Workshop, AIDS and NAIDS are intensely synergistic. AIDS-induced malnutrition can lead to the secondary development of NAIDS, with its much broader array of additional immunological dysfunctions. The complex and far reaching insults to the immune system caused by NAIDS, and the synergistic combination of NAIDS and AIDS, thereby hasten the demise of many victims of AIDS. Aggressive nutritional support for children with HIV infections could delay, or lessen, the development of NAIDS and avoidance of NAIDS would improve both quality and length of life.

Infection-induced malnutrition, the most common form of cytokine-induced malnutrition, results from the actions of proinflammatory cytokines, ie, tumor necrosis factor (TNF) and interleukins 1,6, and 8 (IL-1, IL-6, and IL-8). During acute generalized infections, these cytokines initiate the acute-phase reaction. This reaction is quite stereotyped, and includes fever, malaise, myalgia, headaches, cellular hypermetabolism, and multiple endocrine and enzyme responses. In addition, there is heightened catabolism of muscle proteins and many amino acids; flux of free amino acids into the liver; hepatic synthesis of acute-phase plasma proteins; sequestration of iron and zinc; gluconeo-genesis; insulin resistance; impaired cellular uptake of fatty acids from plasma triglycerides; sizable losses of body nitrogen, potassium, magnesium, phosphate, and zinc; retention of body salt and water; heightened metabolic degradation and/or loss of vitamins; and an activation of the immune system. The pathogenesis of cytokine-induced malnutrition is thus vastly different from the malnutrition caused by uncomplicated starvation. Cytokine-induced malnutrition can have a devastating effect on the immune system and its functions. Although proinflammatory cytokines are found in mucosal fluids, where they contribute to the pathogenesis of inflammatory bowel diseases, it is not known whether cytokines play a role in toxigenic, secretory diarrheas such as cholera, which cause huge losses of body water, electrolytes, and bicarbonate while exhibiting no systemic manifestations of an acute-phase reaction.

A 1972 Paper Describing Multiple Functional Derangements in the Immune System of Indian Children with Generalized Malnutrition.

Annals of the New York Academy of SciencesVolume 587, Issue 1 p. 5-8 Part I. Overview and Vitamins Vitamins and the Immune System WILLIAM R. BEISEL, Corresponding Author WILLIAM R. BEISEL Department of Immunology and Infectious Diseases School of Hygiene and Public Health The Johns Hopkins University Baltimore, Maryland 21205Address for correspondence: William R. Beisel, M.D., F.A.C.P., 8210 Ridgelea Court, Frederick, MD 20701.Search for more papers by this author WILLIAM R. BEISEL, Corresponding Author WILLIAM R. BEISEL Department of Immunology and Infectious Diseases School of Hygiene and Public Health The Johns Hopkins University Baltimore, Maryland 21205Address for correspondence: William R. Beisel, M.D., F.A.C.P., 8210 Ridgelea Court, Frederick, MD 20701.Search for more papers by this author First published: 01 June 1990 https://doi.org/10.1111/j.1749-6632.1990.tb00127.xCitations: 11AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1Perla, D. & J. Marmorston. 1941. Natural Resistance and Clinical Medicine. 908–1091. Little, Brown & Co. Boston, MA. Google Scholar 2Axelrod, A. E., B. Carter, R. H. McCoy & R. Geisinger. 1947. Circulating antibodies in vitamin-deficiency states: I. Pyridoxine, riboflavin, and pantothenic acid deficiencies. Proc. Soc. Exper. Biol. Med. 66: 137–140. 10.3181/00379727-66-16010 CASPubMedWeb of Science®Google Scholar 3Ludovici, P. P. & A. E. Axelrod. 1951. Circulating antibodies in vitamin-deficiency states. Pteroylglutamic acid, niacin-tryptophan, vitamin B12, A, and D deficiencies. Proc. Soc. Exper. Biol. Med. 77: 526–530. 10.3181/00379727-77-18836 CASPubMedWeb of Science®Google Scholar 4Trakatellis, A. C. & A. E. Axelrod. 1969. Effect of pyridoxine deficiency on the induction of immune tolerence in mice. Proc. Soc. Exp. Biol. Med. 132: 46–49. 10.3181/00379727-132-34145 PubMedWeb of Science®Google Scholar 5Axelrod, A. E. 1971. Immune processes in vitamin deficiency states. Am J. Clin. Nutr. 24: 265–271. CASPubMedWeb of Science®Google Scholar 6Beisel, W. R. 1982. Single nutrients and immunity. Am J. Clin. Nutr. 35 (Feb. Suppl.): 417–468. CASPubMedWeb of Science®Google Scholar 7Hodges, R. E., W. B. Bean, M. A. Ohlson & R. E. Bleiler. 1962. Factors affecting human antibody response. IV. Pyridoxine deficiency. Am. J. Clin. Nutr. 11: 180–186. CASPubMedWeb of Science®Google Scholar 8Hodges, R. E., W. B. Bean, M. A. Ohlson & R. E. Bleiler. 1962. Factors affecting human antibody response. V. Combined deficiencies of pantothenic acid and pyridoxine. Am. J. Clin. Nutr. 11: 187–199. CASPubMedWeb of Science®Google Scholar 9 R. M. Suskind, (Ed.) 1977. Malnutrition and the Immune Response. Raven Press. New York, NY. Google Scholar 10Chandra, R. K. & P. M. Newberne. 1977. Nutrition, Immunity, and Infection. Mechanisms of Interactions. Plenum Press. New York, NY. Google Scholar 11Beisel, W. R., R. Edelman, K. Nauss & R. M. Suskind. 1981. Single nutrient effects on immunological functions. J. Am. Med. Assoc. 254: 53–58. Google Scholar 12Minghetti, P. P. & A. W. Norman. 1988. 1,25(OH)2-Vitamin D3 receptors: gene regulation and genetic circuitry. FASEB J. 2: 3045–3053. Google Scholar 13Beisel, W. R. 1988. Use of animals for the study of relations between nutrition and infectious diseases. In Use of Animal Models for Research in Human Nutrition. A. C. Beynem & C. E. West, Eds. Comp. Anim. Nutr. Vol. 6: 33–55. Karger. Basel. Google Scholar 14Smith, S. M. & C. E. Hayes. 1987. Contrasting impairments in IgM and IgG responses of vitamin A-deficient mice. Proc. Natl. Acad. Sci. USA 84: 5878–5882. [Immunology]. 10.1073/pnas.84.16.5878 CASPubMedWeb of Science®Google Scholar Citing Literature Volume587, Issue1Micronutrients and Immune Functions. Cytokines and MetabolismJune 1990Pages 5-8 ReferencesRelatedInformation

Previous articleNext article No AccessNew Biological BooksNutrition and Immunology. Contemporary Issues in Clinical Nutrition, Volume 11. Ranjit K. Chandra William R. BeiselWilliam R. Beisel Search for more articles by this author PDFPDF PLUS Add to favoritesDownload CitationTrack CitationsPermissionsReprints Share onFacebookTwitterLinkedInRedditEmail SectionsMoreDetailsFiguresReferencesCited by The Quarterly Review of Biology Volume 64, Number 1Mar., 1989 Published in association with Stony Brook University Article DOIhttps://doi.org/10.1086/416221 Copyright 1989 Stony Brook Foundation, Inc.PDF download Crossref reports no articles citing this article.

The National Aeronautics and Space Administration (NASA) conducts a research program in the biological and medical aspects of space flight and funds research proposals submitted by interested scientists. Changes that could influence immune status and possibly impair host resistance to infections have been noted and are summarized in a report prepared by the Life Sciences Research Office of the Federation of American Societies for Experimental Biology and a working group of eminent scientists.

Mice with generalized influenza or tularemia of similar lethality were studied in an effort to compare biochemical responses of the myocardium during infections of viral and bacterial etiology. A progressive loss of body weight characterized the course of both infections. Accompanying this, the myocardial content of protein and the activities of lactate dehydrogenase, citrate synthase, and cytochrome c oxidase all decreased. However, myocardial protein degradation appeared earlier and was more pronounced in influenza, and the protein changes were accompanied by a rapid decline of myocardial RNA. Activation of acid hydrolases, such as cathepsin D and beta-glucuronidase, occurred in tularemia but not in influenza, whereas leakage of beta-glucuronidase into the plasma occurred in both infections. Conversely, there was a considerably greater activation of myocardial catalase in influenza. These findings suggested that different control mechanisms or metabolic pathways were operative in the degradation of myocardial constituents in influenza as compared with tularemia. The absence of histological signs of myocarditis in either infection appeared to exclude any direct local effects of an inflammatory process on myocardial cells. Since the infections were of comparable lethality (based upon the inoculated dose of organisms), the observed differences in pattern and extent of metabolic responses of the myocardium to these infections may be attributed to different pathophysiological mechanisms evoked by the different microorganisms.

The accelerated catabolism of skeletal-muscle protein that accompanies severe trauma or infection can now be ascribed to the actions of endogenously produced mediators. Two noteworthy studies described1 , 2 in this issue of the Journal have identified these actions by using in vitro preparations of rat skeletal muscle in a bioassay. Rates of proteolysis in muscle preparations were determined by measuring the release of free amino acid into the medium.Clowes et al.1 isolated and partially characterized a small glycopeptide from the plasma of patients with sepsis or trauma. When compared with control samples of normal plasma, samples containing the mediator were . . .

Previous studies with bacterial infections have demonstrated a reduced exercise capacity and equally pronounced catabolic responses in red and white skeletal muscle. In the present study, red skeletal muscle and heart ventricular muscle were compared in a S. typhimurium model in rats. Two days before median lethality was achieved, the activities of one oxidative (cytochrome c oxidase), one glycolytic (glyceraldehyde-3-phosphate dehydrogenase) and one lysosomal (beta-glucuronidase) enzyme were determined in the two tissues. The contents of protein, RNA and DNA were also determined. The oxidative and glycolytic capacity decreased 24-29% in red skeletal muscle but only 7-20% in the myocardium. However, the decrease in oxidative capacity in skeletal muscle and myocardium was statistically correlated. The protein synthetic capacity (RNA) also decreased and was correlated to the protein concentration in both tissues. This metabolic impairment of both skeletal and heart muscle probably contributes to the deterioration of the physical performance capacity previously observed to follow acute infectious diseases. This study emphasizes the importance of the choice of reference, such as 'wet' weight, DNA or the entire organ, when evaluating metabolic results in biologic tissues and that biochemical alterations in skeletal muscle biopsies in bacterial infections do not reflect alterations in myocardium reliably.