Patterns of co-association of C-reactive protein and nitric oxide in malaria in endemic areas of Iran

Abstract

In addition to numerous immune factors, C-reactive protein (CRP) and nitric oxide (NO) are believed to be molecules of malaria immunopathology. The objective of this study was to detect CRP and NO inductions by agglutination latex test and Griess microassay respectively in both control and malaria groups from endemic areas of Iran, including Southeastern (SE) (Sistan & Balouchestan, Hormozgan, Kerman) and Northwestern (NW) Key words: C-reactive protein -Iran -nitric oxide -malaria -Plasmodium Malaria is a world wide problem and it still remains as a concern in the Eastern Mediterranean region and in Iran (Sadrizadeh 1999, WHO 2003. Iran was divided into two malaria zones, North and South of the Zagros Range of Mountains (Manouchehri et al. 1992), including Southeastern (SE) and Northwestern (NW) provinces (Zakeri et al. 2004, Nahrevanian et al. 2006. The prevalent species is Plasmodium vivax followed by Plasmodium falciparum (Zaim 1987, Edrissian 2002 and mixed-infections (Assmar et al. 2003). Out of 23,562 malaria cases have been reported in the country in 2003, more than 70% occurred in the SE part (Zakeri et al. 2002, WHO 2003. Recently, a new threat of imported malaria emerged from the NW part of the country, Parsabad area, which was affected by a serious epidemic of P. vivax (Sadrizadeh 1999). To date, the malaria situation in SE corner is serious (Zakeri et al. 2002). However, in other endemic areas, malaria is hypoendemic with uncomplicated cases (Edrissian et al. 1993). A malaria eradication programme began in Iran in 1949 and changed to malaria control in 1985 as a result of constraints and challenges. In the SE provinces, the major peak of malaria transmission occurs between September and November, with 21% of malaria cases in this region caused by P. falciparum (WHO 2004). Chloroquine (CQ) is still being recommended as the first-line treatment for uncomplicated cases of P. falciparum malaria, with a combination of sulfadoxine-pyrimethamine and quinine recommended for the CQ treatment failures. Increased drug and insecticide resistance has made vaccine preparation urgent for malaria with a focus on new immune targets. Potential mechanisms of immunity against malaria include antibodies, cytotoxic T-cells, cytokines and a variety of other soluble mediators. Macrophages are key components of the antimicrobial immune responses, generating large amounts of toxic molecules, reactive oxygen and nitrogen intermediates (RNI), H 2 O 2 and nitric oxide (NO) (Bogdan et al. 2000). In addition to NO, C-reactive protein (CRP) is a major acute phase protein present in normal serum, which increases significantly after most forms of tissue injuries and infections as a non-specific innate defense mechanism of the host. CRP as a protein is mainly regulated at the transcriptional level induced by cytokines (Kremsner et al. 1996, Ablij & Meinders 2002. It is a marker of inflammatory reactions and cytokine activation (Jakobsen et al. 1998), which is produced very early after infection (McCarty et al. 2004). Besides CRP ...

Oxidative and Nitrosative Stress on Phagocytes’ Function: from Effective Defense to Immunity Evasion Mechanisms

“…Still considering malaria, weaker NO production by macrophages was associated with a worst outcome of cerebral malaria (Gramaglia et al 2006;Lopansri et al 2003), indicating that NO is essential in parasite killing, confirming previous reports (Balmer et al 2000;Nahrevanian 2006;Nahrevanian et al 2008). However, excessive amounts of NO and peroxynitrite can aggravate infections, explaining why NO overload could also be toxic, especially to the brain (Ferrari et al 2009;Nahrevanian 2006;Nahrevanian et al 2008). In fact, NO decreases expression of intercellular and vascular cell adhesion molecules inhibiting P. falciparum adhesion to endothelium of brain vessels, but the parasite induces release of IgE and subsequent NO overload which aggravates cerebral malaria (Mazie and Idrissa-Boubou 1999).…”

“…Lacking of NO synthesis from leucocyte phagocytes is associated with increased risk of infection by Porphyromonas gingivalis (Gyurko et al 2003), Trypanosoma cruzi (Hölscher et al 1998;Talvani et al 2002), and P. falciparum (Boutlis et al 2003). Still considering malaria, weaker NO production by macrophages was associated with a worst outcome of cerebral malaria (Gramaglia et al 2006;Lopansri et al 2003), indicating that NO is essential in parasite killing, confirming previous reports (Balmer et al 2000;Nahrevanian 2006;Nahrevanian et al 2008). However, excessive amounts of NO and peroxynitrite can aggravate infections, explaining why NO overload could also be toxic, especially to the brain (Ferrari et al 2009;Nahrevanian 2006;Nahrevanian et al 2008).…”

Involvement of nitric oxide and its up/down stream molecules in the immunity against parasitic infections

“…It is suggested that the detrimental effect of NOS is related to the L-arginine and NO concentrations, because NO at high concentration has a clear anti-inflammatory effect [139][140][141][142]. Thus, activation of NO could be a potential therapeutic strategy to suppress parasitic infections [143][144][145]. Nevertheless, the functional role of NO and NOS isoforms in the immune responses of host against the majority of parasites is still highly controversial.…”

Partial Immunotherapy of Leishmaniasis by in vivo Trial of L-Arginine in Balb/c Mice Infected with Leishmania major via Nitric Oxide Pathway

“…As L-Arg has long been identified as an essential amino acid for Leishmania growth, promastigotes could not be maintained in L-Arg-free media (Krassner and Flory, 1971), suggesting mechanisms of L-Arg uptake and utilization in Leishmania parasites (Shaked-Mishan et al, 2006). This study is a continuous research of authors previous publications (Nahrevanian, 2004(Nahrevanian, , 2006Nahrevanian and Amini, 2009;Nahrevanian et al, 2006Nahrevanian et al, , 2008Nahrevanian et al, , 2009a2009b). Therefore, the aim of this study is to investigate the partial immunotherapy of leishmaniasis by in vivo trial of L-Arg in Balb/c mice infected with Leishmania major via nitric oxide pathway.…”