LA MEDIACION EN EL ECUADOR

Interleukin-10 produced by monocytes, Th2, and B-cells inhibits cytokine production in Th1 and CD8+ cells but not in Th2 cells. Though interleukin-10 does not affect the proliferation of Th1 and CD8+ cells, it induces B-cell proliferation and immunoglobulin production, which is essential for the development and maturation of antimalarial antibodies. Interleukin-10 seems to have an important role in defining the T helper cell response to malaria. Interleukin-10 decrease antigen presentation by the down regulation of MHC class II molecules on macrophages (Akdis and Blaser, 1999). Interleukin-10 synthesis inhibits interferon-γ and TNF-α secretion and this has been shown to be important to counteract macrophage induced pathology in cerebral malaria (Kossodo et al., 1997)

Interleukin-10 has been reported in the plasma of patients with acute malaria (Wenisch et al., 1995). In malaria patients, an increased ratio between TNF-α and interleukin-10 contributes to reversible bone-marrow suppression (Othoro et al., 1999) and severe anaemia has been associated with reduced concentrations of circulating interleukin-10 (Kurtzhals et al., 1998). It has been shown that in patients with malaria parasitaemia , increase of interleukin-10 is more pronounced and more specific than interleukin-6 and interleukin-8 compared to patients with other infections(Jason et al., 2001). The increased concentrations of interleukin-10 may have a beneficial role as an immunoregulatory cytokine by reducing the parasite-induced inflammatory response. The importance of immune cell effectors and associated cytokines during the presentation of various malaria parasite stages and their general role in the management of the host's immune response to malaria has been, and continues to be, under investigation. However, abnormal macrophage activation and anti-inflammatory, as well as pro-inflammatory, cytokines

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may be associated with heightened disease severity and mortality of malaria, most likely by stimulating other factors such as NOI and ROI. Understanding the cytokine interactions that produce both control and pathology will be helpful in the design of future immune treatment to prevent millions of malarial deaths in future generations.

2.6.4 Interaction between the endocrine system and immune responses during malaria infection

Immune system does not work in isolation as immune, endocrine, and central nervous systems are integrated through a network of signal molecules (cytokines, hormones, and neurotransmitters) that act on a common set of receptors. It is influenced by many other factors that may be neuroendocrine peptides, sex hormones, or other metabolites. In certain cases, hormones can regulate the innate immune response and the subsequent adaptive immune response (Hernández-Bello et al., 2010). For example, in general, estrogen (E2) exerts different effects on T-lymphocytes by altering cytokine production and modulating cell proliferation.

At low concentrations, E2 promotes the Th1 response and cell-mediated immunity but at high concentration augment Th2 responses and humoral immunity (Straub, 2007). E2 can primaryalso remarkably exert in a concentration-dependent manner a proinflammatory or anti- cytokines and increases leukocyte migration to sites of inflammation (Straub, 2007). However, at high levels, E2 inhibits cell-mediated immunity and decreases the expression of activation markers (Attanasio et al., 2002; Enomoto et al., 2007). It also inhibits TNF-α, IL-1β, and IL-6 production by T cells, macrophages, and DCs but induces Th2-type cytokines, such as 4, IL-10, and TGF-β, resulting in anti-inflammatory effects (Zang et al., 2002). E2 peak levels reduce Th1type cytokine production (TNF-α and IFN-γ) by T cells, macrophages, and DCs (Härkönen

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and Väänänen, 2006; Salem et al., 2000; Straub, 2007) but enhances antibody production by enhancing IL-10 in human peripheral blood mononuclear cells (Kanda and Tamaki, 1999)

The increased susceptibility of pregnant women to malaria is thought to be due either to sequestration of parasites in the placenta or to depression of selective components of the immune system in association with increased production of several hormones or proteins. The production of hormones and other pregnancy regulatory factors in primigravidae may alter cell function, thereby conferring an advantage for malarial infection. Cortisol and estrogens have been shown to depress the cellular immune response during pregnancy (Bouyou-Akotet et al., 2004; Brabin, 1997) Some studies have demonstrated that glucose levels increase during both uncomplicated and severe malaria, mostly due to increase rate of gluconeogenesis (Dekker et al., 1997; van Thien et al., 2001). Therefore, cortisol has a major role in the increase of glucose levels in malaria patients. Plasma corticoid levels regulate the effector part of immunity against several pathogens, and elevated plasma corticoid levels decrease the number of circulating lymphocytes and monocytes, which are important for control of malaria (Thomson et al., 1980).

Cortisol reduces the adherence of infected erythrocytes to monocytes (Goldring and Ramoshebi, 1999)The cortisol concentration is inversely related to mononuclear cell proliferation in response to malarial antigens in primigravidae from the Gambia (Goldring and Ramoshebi, 1999). Data from some studies demonstrated that high cortisol concentrations reduce NK cell cytoxicity against P. falciparum infected red blood cells (Bouyou-Akotet et al., 2004), and down regulates the surface expression of specific cytotoxic receptors on NK cells (natural cytotoxic receptors:

NCR) (Mavoungou et al., 2005), thus showing the important role of cortisol in the depression of cell-mediated immunity responsible for the increase susceptibility of primigravidae to malaria(Bouyou-Akotet et al., 2005). A positive correlations between cortisol concentrations and

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P. falciparum infection, on the one hand, and parasite load, on the other hand confirms a causal relationship between high cortisol levels and increased susceptibility to malaria in primiparous women(Bouyou-Akotet et al,2005)

All of these data suggest the parasites exploit the endocrine mechanisms of the host for its own advantage. There is need to elucidate the immunoendocrine interactions during parasite infections because of its importance in understanding the mechanisms involved in parasite establishment, growth, and reproduction in human hosts. A deeper comprehension of this complex relationship could have implications in the control and treatment of various infections throughout the world. The physiologic elements that are essential in the network of immunoendocrine interactions during parasite infection could have a deep biological and physiopathological impact. Thus, a better understanding could be extremely valuable in designing vaccines and new antiparasitic drugs and in controlling various human and veterinary parasitosis.

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CHAPTER THREE

MATERIALS AND METHODS 3.1 STUDY AREA

This study was conducted in primary health facilities in Lagos State. Lagos state is an African megacity located in south-western Nigeria on the west coast of Africa, within latitudes 6023′N and 6041′N and longitudes 2042′E and 3042′E. Lagos State accounts for more than 70% of the nation‘s industrial and commercial establishments. Physically it is the smallest but most highly populated state in the country, with an estimated population of over 20 million inhabitants, which is more than 10% of the total population in Nigeria (Iwugo et al., 2003) Lagos state shares boundary with Ogun state both in the north and east and is bounded on the west by the Republic of Benin. In the south it stretches for 180 kilometres along the coast of the Atlantic Ocean.

Lagos is a low-lying coastal State and is Nigeria‘s centre of commerce with very diverse and fast-growing population, resulting from heavy and on-going migration to its cities from all parts of Nigeria as well as neighbouring and foreign countries. Lagos state has 20 local government areas and 37 local council development areas (LCDA), it was the Capital City of the country before it was moved to Abuja on the 12^th of December, 1991. The land surface in the state generally slopes gently downwards from north to south and is naturally made up of depositional landforms which include: wetlands, barrier islands, beaches, low-lying tidal flats and estuaries (Iwugo et al., 2003).

Transmission of malaria is moderate and stable in Lagos but peaks during the wet season corresponding to increase in the population of mosquitoes. Lagos has been described as mesoendemic during the dry season (Aina et al., 2013).