L-Arginine reverses radiation-induced immune dysfunction: the need for optimum treatment window

Radiat Res. 2009 Feb;171(2):180-7. doi: 10.1667/RR1241.1.


The aim of the present study was to investigate the protective efficacy of l-arginine in mitigating the injury induced by 2 Gy of total-body gamma radiation (TBI). Mice exposed to radiation (TBI group) had significantly decreased spleen weight, splenocyte numbers and bone marrow cellularity. Administration of l-arginine 2 h after TBI (TBI + l-arginine group) was effective in reducing the radiation-induced depletion of spleen and bone marrow cellularity but was not effective when administered before TBI (l-arginine + TBI group). The radiation-induced decrease in Con A-induced spleen cell proliferation, specific antibody response of spleen B cells to sheep red blood cells, and spleen RNA content was reversed in mice in the TBI + l-arginine group. The radiation-induced increase in serum TNF-alpha levels, serum nitrate/nitrite (NOx) levels, spleen DNA fragmentation, spleen nitric oxide synthase (NOS) activity, spleen inducible NOS (iNOS) activity, and hepatic iNOS activity was reversed in mice in the TBI + l-arginine group. l-Arginine administered before TBI could not reverse these changes. Mice in the TBI + l-arginine group had significantly increased spleen arginase activity compared to mice from either the TBI or l-arginine + TBI group. The results suggest the importance of the time of administration of l-arginine and the l-arginine pathway in mitigating the radiation-induced host immune dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine / therapeutic use*
  • Base Sequence
  • Cell Proliferation / drug effects
  • DNA Primers
  • Immune System Diseases / drug therapy*
  • Immune System Diseases / etiology
  • Male
  • Mice
  • Nitric Oxide Synthase Type II / metabolism
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / enzymology
  • Spleen / radiation effects
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / radiation effects
  • Tumor Necrosis Factor-alpha / metabolism
  • Whole-Body Irradiation / adverse effects*


  • DNA Primers
  • Tumor Necrosis Factor-alpha
  • Arginine
  • Nitric Oxide Synthase Type II