Immunodeficiency associated with anorexia nervosa is secondary and improves after refeeding

Several studies have addressed the question of starvation effects on immune function by means of changes in lymphocyte subsets, cytokine induction or lymphocyte activation. Anorexia nervosa (AN) patients are severely malnourished and contradictory results have been obtained regarding the accompanying immunodeficiency, including its assignation as a part of the primary nervous disorder. In the present work, an extensive immunological function examination was carried out on 40 AN patients who were compared with a control group of 14 healthy girls. The AN patients were also classified according to their nutritional status (by the Body Mass Index: BMI), this being critical for a better understanding of these secondary immunodeficiency bases. Moreover, another immune system study was performed on five patients after refeeding. Lymphocyte subsets and function, cytokine induction and peripheral blood concentrations, and innate as well as humoral immunity were evaluated. Deregulation in the cytokine network, owing to the interaction of the central nervous (CNS) and immune systems, seems to be the initial immune alteration in AN immunodeficiency but it has not been disproved that the immunodeficiency is a direct consequence of the original psychiatric perturbation. Spontaneous high levels of circulating interleukin‐1β (IL‐1β) and tumour necrosis factor‐α (TNF‐α) have been observed; this is probably one of the causes of the anomalies found in the T‐cell subpopulations (mainly the naive CD4+CD45RA+ reduction and the cytotoxic CD8+ increase) and T‐cell activation status (mainly the down‐regulation of the CD2 and CD69 activation pathways). This finally leads to an impairment, not only in T‐cell function but also in T‐cell to B‐cell co‐operation. The AN specificity of these results is confirmed by the fact that these immune alterations improve after refeeding and when nutritional status becomes less critical, which also suggests that AN immunodeficiency is indeed secondary to malnutrition.

[1]  C. Dinarello,et al.  Increased plasma interleukin-1 activity in women after ovulation. , 1985, Science.

[2]  A. R. Lucas.  On the meaning of laboratory values in anorexia nervosa. , 1977, Mayo Clinic proceedings.

[3]  R. Dantzer,et al.  Stress and immunity: an integrated view of relationships between the brain and the immune system. , 1989, Life sciences.

[4]  H. Moldofsky,et al.  Hypothalamic-pituitary function in anorexia nervosa. , 1975, Archives of general psychiatry.

[5]  M. Sanders,et al.  Human naive and memory T cells: reinterpretation of helper-inducer and suppressor-inducer subsets. , 1988, Immunology today.

[6]  M. Dardenne,et al.  Thymulin (Zn-facteur thymique serique) activity in anorexia nervosa patients. , 1985, The American journal of clinical nutrition.

[7]  M. O. Landázuri,et al.  An in Vivo Functional Immune System Lacking Polyclonal T‐Cell Surface Expression of the CD3/Ti(WT31) Complex , 1987, Scandinavian journal of immunology.

[8]  A. Arnaiz-Villena,et al.  Brief report: primary immunodeficiency caused by mutations in the gene encoding the CD3-gamma subunit of the T-lymphocyte receptor. , 1992, The New England journal of medicine.

[9]  R. Vigersky,et al.  Anorexia nervosa: behavioural and hypothalamic aspects. , 1976, Clinics in endocrinology and metabolism.

[10]  Lucas Ar.  On the meaning of laboratory values in anorexia nervosa. , 1977 .

[11]  R. Watson,et al.  Effect of renutrition on humoral and cell-mediated immunity in severely malnourished children. , 1981, The American journal of clinical nutrition.

[12]  A. Sommer,et al.  Abnormal T-cell subset proportions in vitamin-A-deficient children , 1993, The Lancet.

[13]  D L Udelman,et al.  Stress and immunity. , 1982, Psychotherapy and psychosomatics.

[14]  S. Ward.  CD28: a signalling perspective. , 1996, The Biochemical journal.

[15]  C. Caldwell,et al.  A rapid, no-wash technic for immunophenotypic analysis by flow cytometry. , 1986, American journal of clinical pathology.

[16]  M. Crumpton,et al.  The CD2 antigen associates with the T-cell antigen receptor CD3 antigen complex on the surface of human T lymphocytes , 1989, Nature.

[17]  S. Ziegler,et al.  The activation antigen CD69 , 1994, Stem cells.

[18]  A. R. Lucas,et al.  An immunological assessment of patients with anorexia nervosa. , 1981, The American journal of clinical nutrition.

[19]  A. Crisp.  Anorexia nervosa 'feeding disorder', 'nervous malnutrition' or 'weight phobia'? , 1970, World review of nutrition and dietetics.

[20]  M. Salmon,et al.  The synergy between naive and memory T cells during activation. , 1991, Immunology today.

[21]  F. Marci.  [The role of nutrition]. , 1992, Minerva stomatologica.

[22]  M. Plebanski,et al.  Dependency on interleukin‐1 of primary human in vitro T cell responses to soluble antigens , 1992, European journal of immunology.

[23]  A. Marcos,et al.  Nutritional status and immunocompetence in eating disorders. A comparative study. , 1993, European journal of clinical nutrition.

[24]  K. Frei,et al.  Production of hemopoietic colony-stimulating factors by astrocytes. , 1990, Journal of immunology.

[25]  M Peakman,et al.  T lymphocyte subpopulations in anorexia nervosa and refeeding. , 1997, Clinical immunology and immunopathology.

[26]  S. H. Socher,et al.  Recombinant human tumor necrosis factor induces acute reductions in food intake and body weight in mice , 1988, The Journal of experimental medicine.

[27]  J. Jenkins,et al.  Hypothalamic-pituitary function in anorexia nervosa. , 1975, Acta endocrinologica.

[28]  J. Dayer,et al.  Cell surface glycoproteins expressed on activated human T cells induce production of interleukin-1 beta by monocytic cells: a possible role of CD69. , 1993, European cytokine network.

[29]  E. Opara,et al.  Tumor necrosis factor-α and total parenteral nutrition-induced anorexia* , 1995 .

[30]  P. Newberne,et al.  Role of nutrition in immunologic function. , 1980, Physiological reviews.

[31]  R. Grimble.  Nutrition and Cytokine Action , 1990, Nutrition Research Reviews.

[32]  A. Arnaiz-Villena,et al.  Retinol (vitamin A) is a cofactor in CD3‐induced human T‐lymphocyte activation , 1997 .

[33]  R. Weizman,et al.  Cytokine production in anorexia nervosa. , 1993, Clinical neuropharmacology.

[34]  M. Kluger,et al.  Endogenous pyrogen activity in human plasma after exercise. , 1983, Science.

[35]  B. Alarcón,et al.  Expression and function of a variant T cell receptor complex lacking CD3-gamma , 1991, The Journal of experimental medicine.

[36]  A. Arnaiz-Villena,et al.  Peripheral blood reduction of memory (CD29+, CD45RO+, and "bright" CD2+ and LFA-1+) T lymphocytes in Papillon-Lefèvre syndrome. , 1994, Human immunology.

[37]  C. Plata-salamán,et al.  Tumor necrosis factor and interleukin-1β: suppression of food intake by direct action in the central nervous system , 1988, Brain Research.

[38]  J. Calabrese,et al.  Alterations in immunocompetence during stress, bereavement, and depression: focus on neuroendocrine regulation. , 1987, The American journal of psychiatry.

[39]  R. P. Thompson,et al.  Cell-mediated immunity in anorexia nervosa. , 1986, Clinical and experimental immunology.

[40]  D. Liggitt,et al.  Development of partial tolerance to the gastrointestinal effects of high doses of recombinant tumor necrosis factor-alpha in rodents. , 1987, The Journal of clinical investigation.

[41]  J. Peyron,et al.  CD3-stimulated Jurkat T cells mediate IL-1 beta production in monocytic THP-1 cells. Role of LFA-1 molecule and participation of CD69 T cell antigen. , 1993, European cytokine network.