Cytokines as determinants of disease and disease interactions

Sher, Alan; Gazzinelli, Ricardo T.; Janković, Dragana; Scharton‐Kersten, Tanya; Yap, George; Doherty, T. Mark; Wynn, Thomas A.

doi:10.1590/s0100-879x1998000100011

Cited by 12 publications

(5 citation statements)

References 9 publications

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“…The suggestion presented here that an exacerbated IFN-␥ secretion can be correlated with the development of the severe cardiac form of the T. cruzi infection has been shown to occur in some intracellular bacterial and protozoan infections, such as Listeria monocytogenes, Toxoplasma gondii, Mycobacterium tuberculosis, and Leishmania major, in which the Th1 response can be protective for the host but can also be detrimental when exacerbated (8,17,27).…”

Section: Discussionmentioning

confidence: 92%

Evidence that Development of Severe Cardiomyopathy in Human Chagas' Disease Is Due to a Th1-Specific Immune Response

et al. 2003

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The role of interleukin 10 (IL-10) and gamma interferon (IFN-␥) on the development of pathology in human Chagas' disease was investigated. Two categories of patients, low and high producers of IFN-␥, were identified based on the levels of secretion of this cytokine in the supernatant of peripheral blood mononuclear cell (PBMC) cultures. Eighty-three percent of the patients presenting with cardiac disease (CARD) of different degrees and 59% of the patients with the indeterminate form of disease (IND) were identified as high IFN-␥ producers. PBMC from IND patients classified as low IFN-␥ producers secreted significantly higher amounts of IL-10 than did those from other groups. Flow cytometry analysis demonstrated that in PBMC from the IND group, the majority of the IL-10-producing cells were monocytes (CD14 High؉ cells), whereas in the CARD group, the major sources of IFN-␥ were T lymphocytes (CD3 ؉ CD4 ؉ cells). These results suggest an association between the production of IFN-␥ by CD3؉ CD4 ؉ cells and morbidity in Chagas' disease, whereas the production of IL-10 by macrophages/monocytes leads to regulation of the immune response in IND patients. We hypothesize that an exacerbated production of IFN-␥ against Trypanosoma cruzi antigens favors the development of a strong Th1 response in CARD patients, which leads to progression of heart disease.

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Section: Discussionmentioning

confidence: 92%

Evidence that Development of Severe Cardiomyopathy in Human Chagas' Disease Is Due to a Th1-Specific Immune Response

et al. 2003

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“…Fourthly, replenishment, which constitutes a separate therapeutic tool, has been achieved with blood or platelet transfusion. Finally, immunomodulation has been approached through different avenues that include cytokine infusions [11,48,[57][58][59][60]. Immunosuppressive therapy has been experimented with in the manipulation of clonal B cell disorders and CD40 receptors.…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

Thrombocytopenia in HIV Disease: Clinical Relevance, Physiopathology and Management

Míguez‐Burbano¹,

Jackson²,

Hadrigan³

2005

CMCCHA

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HIV infection is associated with a myriad of hematopoietic abnormalities. Thrombocytopenia (TCP), the condition in which platelet counts fall below 150x10(3)/mm3 in two or more consecutive platelet counts, is a condition frequently seen in HIV infected individuals regardless of HIV status, gender, or age. Having recently been associated with rapid disease progression, and by complicating the management of AIDS patients, thrombocytopenia has become a medical challenge, highlighting the urgent need for evidence-based treatment protocols in this area. Due to the physiopathology of HIV, therapeutic options currently available for TCP in this already vulnerable population are severely limited. Whereas clinicians often intervene to prevent life-threatening, thrombocytopenia-associated outcomes in the general population, there is no intervention protocol: for the HIV subjects. Management of the condition seems to be the norm for these individuals. As a result, thrombocytopenia in HIV is a subject that is in urgent need of re-examination. In this review, the importance of thrombocytopenia and current knowledge regarding the physiopathology of HIV-associated thrombocytopenia is discussed, and an overview of current and under-investigation treatment approaches to this adverse hematological condition is provided.

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“…Tr1 cells, for example, predominantly produce high levels of IL‐10 [1]. These cells may be involved in host protective and IL‐10‐mediated negative feedback regulation, able to silence both Th1‐ and Th2‐dominated immune responses [2]. So‐called Th3 cells predominantly produce TGF‐β and are implicated in mucosal tolerance in the mouse [3].…”

Section: The Th1/th2 Paradigmmentioning

confidence: 99%

The paradigm of type 1 and type 2 antigen‐presenting cells. Implications for atopic allergy

Kapsenberg

Hilkens

Wierenga

et al. 1999

Clin Experimental Allergy

105

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Optimal clearance of the various pathogen types encountered by the human body requires the selective activation of particular cellular and/or humoral immune responses. The orchestration of the types of effector responses is directed by Th cells through the production of type 1 (Th1 cell‐associated) and type 2 (Th2 cell‐associated) cytokines. The way in which the Th cell cytokine profile is matched to the type of invading pathogen, and why these profiles sometimes derail and lead to disease, is not well understood. Here, we will discuss the concept that antigen‐presenting cells (APC) provide Th cells not only with antigen and costimulatory signals, but also with a polarizing signal (signal 3). This signal can be mediated by many APC‐derived factors, but IL‐12 and PGE2 seem to be of major importance. The Th2‐biased responses in atopic allergy appeared to be associated with monocytes with a decreased IL‐12/PGE2 ratio and, consequently, with the down‐regulation of type 1 cytokine production in Th cells. As for Th cells, APC can be functionialy polarized. In vitro experiments with monocyte‐derived dendritic cells (DC) showed that the presence of IFN‐γ during activation of immature DC primes for mature DC with the ability of high IL‐12 production and, consequently, a Th1‐driving capacity (APC1 or DC1). In contrast, PGE2 primes for a low IL‐12 production ability and a Th2‐driving capacity (APC2 or DC2). These findings suggest that pathogens provoke either Th1‐ or Th2‐cell development by inducing the production of a certain pattern of inflammatory DC‐polarizing mediators (e.g. IFN‐γ and PGE2) at the site of infection. The type of immune polarization will not only depend on the type of pathogen, but also varies with the type of infected tissue, i.e. that different tissues produce different mediators in response to the same pathogen. In the case of atopic allergy, this concept implies that the Th2‐cell bias may be related to low levels of cross‐regulatory infections, to Th1 cell‐inducing pathogens, or to an aberrant function of stromal cells in peripheral tissues.

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Cytokines as determinants of disease and disease interactions

Cited by 12 publications

References 9 publications

Evidence that Development of Severe Cardiomyopathy in Human Chagas' Disease Is Due to a Th1-Specific Immune Response

Evidence that Development of Severe Cardiomyopathy in Human Chagas' Disease Is Due to a Th1-Specific Immune Response

Thrombocytopenia in HIV Disease: Clinical Relevance, Physiopathology and Management

The paradigm of type 1 and type 2 antigen‐presenting cells. Implications for atopic allergy

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