Impairment of macrophage activation and granuloma formation by protein deprivation in mice

Cell Immunol. 1992 Feb;139(2):493-504. doi: 10.1016/0008-8749(92)90088-7.


Protein-calorie malnutrition predisposes to infection by intracellular pathogens, but the basis for this predisposition is unclear. We studied the effect of protein deprivation on mouse peritoneal macrophage function and on granuloma formation during infection by bacille Calmette-Gueŕin (BCG). Injection of lipopolysaccharide (LPS) to induce inflammation elicited fewer peritoneal cells from mice fed a 2.5% protein diet than from mice fed an isocaloric chow in which protein calories constituted 24% of the total. LPS-elicited macrophages from protein-deprived mice demonstrated a reduction in spreading, total cell protein, cell lactate dehydrogenase, and release of superoxide anion (O2-) in response to stimulation. Priming in vitro by interferon (IFN)-gamma for enhanced release of O2- was also significantly impaired in protein-deprived mice. This defect was reversible by repletion with 24% protein diet for 10 days. Impairment of macrophage function in protein-deprived mice was further evidenced by an impaired capacity to express Ia antigen in response to IFN-gamma and by reduced production of IL-1 activity in response to LPS. Infection by BCG in protein-deprived mice was characterized by impaired granuloma development in liver, lungs, and spleen. Thus, in this model, protein deprivation significantly impaired macrophage activation, as assessed by morphologic, metabolic, and functional criteria. This impairment might compromise immune effector mechanisms dependent on macrophage activation, including rejection of intracellular pathogens.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • Disease Models, Animal
  • Granuloma / immunology
  • Histocompatibility Antigens Class II / analysis
  • Histocompatibility Antigens Class II / biosynthesis
  • Interleukin-1 / analysis
  • Interleukin-1 / metabolism
  • Lipopolysaccharides
  • Macrophage Activation / immunology*
  • Macrophages / immunology*
  • Male
  • Mice
  • Protein Deficiency / immunology*
  • Superoxides / analysis


  • Histocompatibility Antigens Class II
  • Interleukin-1
  • Lipopolysaccharides
  • Superoxides