The role of nitric oxide in the immune system

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Nitric oxide is produced in high amount from the break down of arginine by a group of enzyme called nitric oxide synthase. Nitric oxide is an intercellular messenger that has been recognized as one of the versatile player in the immune system. Cells of the innate immune system such as macrophages, neutrophil and natural killer use pattern recognition receptors to recognize the molecular patters associated with pathogens. The specific role nitric oxide plays depend on the place of its release which in the immune system inhibits the replication of bacteria.

Chapter One


Background of the Study

During the past two decades, nitric oxide (NO) has been recognized as one of the most versatile players in the immune system. It is involved in the pathogenesis and control of infectious diseases, tumors, autoimmune processes and chronic degenerative diseases. For the first time, Mitchell et al. (1916) reported that mammalian cells produced oxides of nitrogen. Tannenbaum and co-workers (1983) demonstrated that mammalian cells were producing nitrate (NO3-), and its production could be enhanced by endotoxin treatment. In 1985 NO formally entered the immunology scene for its role in the immune system. NO is a vasodilator, diatomic free radical, lipid soluble that reacts with a variety of molecules and mediates a large spectrum of biological effects (Nathan and Hibbs, 1991).

NO production is a feature of genuine immune-system cells (dendritic cells, NK cells, mast cells and phagocytic cells including monocytes, macrophages, microglia, Kupffer cells, eosinophils and neutrophils) as well as other cells involved in immune reactions (endothelial cells, epithelial cells, vascular smooth muscle cells, fibroblasts, keratinocytes, chondrocytes, hepatocytes, mesangial cells and Schwann cells (Bogdan, 2000). The production of NO has been thoroughly documented in cattle immune cells such as macrophages (Stuehr and Nathan, 1989), lymphocytes (Kirk et al., 1990; Reiling et al., 1996; Dixit and Parvizi, 2001) and blood leukocytes (Boulanger et al., 2001). Overproduction of NO has been observed in several inflammatory diseases. Among its many immunomodulatory properties, nitric oxide is a potent inhibitor of lymphocyte proliferation.

Several studies (Kirk et al., 1990; Reiling et al., 1996; Henson et al., 1999; Dixit and Parvizi, 2001; Boulanger et al., 2001) in bovines have shown that NO is liberated either spontaneously or after cleavage by ecto-enzymes found on T and B lymphocytes. MacMicking et al., (1997) reported that NO regulated T cell proliferation, cytokine production, apoptosis and cell signaling activity in vivo and in vitro by iNOS (inducible nitric oxide synthase) expression in immune cells. Counjun et al., (2004) reported that peripheral blood lymphocytes in bovines are capable of expressing iNOS enzyme which helps to produce NO. Bovine immune cells that are capable of expressing iNOS include macrophages (Adler et al., 1995), blood leukocytes (Boulanger et al., 2001) and lymphocytes (Dixit and Parvizi,

Statement of the problem

It has become increasingly apparent in recent years that NO and reactive nitrogen intermediates (nitrite and peroxynitrite) are potentially important mediators of the immune system (1). Production of NO by activated murine macrophages has been implicated as an antimicrobial effect or mechanism against several pathogens. Previous reported that macrophage activation produced by vaccination with a whole-cell pertussis vaccine (WCV) is associated with induction of NO synthesis by macrophages in response to in vitro stimulation with B. pertussis antigens. The presence of small quantities of active pertussis toxin seems to be important for this process. The relationship between NO induced in macrophages in response to in vitro culture with bacterial antigens and protection in vivo in the mouse intracerebral challenge model indicates that macrophage activation is involved in protective immunity. However, it is not clear from these studies whether NO is an effector of protection or simply a coincidental marker of activation. To clarify further the role of NO in immunity. The induction of NO synthesis by macrophages and protection in vivo against aerosol challenge induced by a conventional WCV and the new-generation acellular pertussis vaccine (ACV) was investigated in inducible nitric oxide synthase (iNOS)-deficient mice.


The overall aim of this work was to investigate the role of NO in human immunity.

  1. In the clinical setting our first aim was to investigate local and systemic levels of NO in human being.
  2. Our second aim was to assess the effect of NO-production and clinical outcome in sick patients during standard treatment.

Research Questions

  1. What are the local and systemic levels of NO in human being?
  2. What is the effect of NO-production and clinical outcome in sick patients during standard treatment?

Significance of the Study

The findings of this study would be beneficial to the, researchers, Ministry of health, students, and health policy makers. The findings would provide useful information to nitric

This study would also be significant in the sense that its finding would serve as reference materials for future researchers to carry out further studies in the field of knowledge under study

Limitation of the study

In every research work, it is likely that the researcher may encounter some limitations. The researcher encountered some challenges during the period of carrying out this research. Some of these challenges include the dearth of materials for a proper and effective research work constituted a major limitation.


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