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Bayesian modeling suggests that IL-12 (p40), IL-13 and MCP-1 drive murine cytokine networks in vivo.

ABSTRACT: Cytokine-hormone network deregulations underpin pathologies ranging from autoimmune disorders to cancer, but our understanding of these networks in physiological/pathophysiological states remains patchy. We employed Bayesian networks to analyze cytokine-hormone interactions in vivo using murine lactation as a dynamic, physiological model system.Circulatory levels of estrogen, progesterone, prolactin and twenty-three cytokines were profiled in post partum mice with/without pups. The resultant networks were very robust and assembled about structural hubs, with evidence that interleukin (IL)-12 (p40), IL-13 and monocyte chemoattractant protein (MCP)-1 were the primary drivers of network behavior. Network structural conservation across physiological scenarios coupled with the successful empirical validation of our approach suggested that in silico network perturbations can predict in vivo qualitative responses. In silico perturbation of network components also captured biological features of cytokine interactions (antagonism, synergy, redundancy).These findings highlight the potential of network-based approaches in identifying novel cytokine pharmacological targets and in predicting the effects of their exogenous manipulation in inflammatory/immune disorders.

SUBMITTER: Field SL

PROVIDER: S-EPMC4640223 | biostudies-other | 2015 Nov

REPOSITORIES: biostudies-other

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Bayesian modeling suggests that IL-12 (p40), IL-13 and MCP-1 drive murine cytokine networks in vivo.

Field Sarah L SL Dasgupta Tathagata T Cummings Michele M Savage Richard S RS Adebayo Julius J McSara Hema H Gunawardena Jeremy J Orsi Nicolas M NM

BMC systems biology 20151109

<h4>Background</h4>Cytokine-hormone network deregulations underpin pathologies ranging from autoimmune disorders to cancer, but our understanding of these networks in physiological/pathophysiological states remains patchy. We employed Bayesian networks to analyze cytokine-hormone interactions in vivo using murine lactation as a dynamic, physiological model system.<h4>Results</h4>Circulatory levels of estrogen, progesterone, prolactin and twenty-three cytokines were profiled in post partum mice w ...[more]

PMID: 26553024

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Project description:Mycetoma is a neglected tropical disease, endemic in many tropical and subtropical regions, characterised by massive deformity and disability and can be fatal if untreated early and appropriately. Interleukins (IL) -35 and IL-37 are newly discovered cytokines that play an important role in suppressing the immune system. However, the expression of these interleukins in patients with Madurella mycetomatis (M. mycetomatis) induced eumycetoma has not yet been explored. The aim of this study is to determine the levels of IL-1 family (IL-1β, IL-37) and IL-12 family (IL-12, IL-35) in a group of these patients and the association between these cytokines levels and the patients' demographic characteristics. The present, case-control study was conducted at the Mycetoma Research Centre, Soba University Hospital, University of Khartoum, Sudan and it included 140 individuals. They were divided into two groups; group I: healthy controls [n = 70; median age 25 years (range 12 to 70 years)]. Group II: mycetoma patients [n = 70 patients; median age 25 (range 13 to 70 years)]. Cytokines levels were measured in sera using enzyme linked immunosorbent assay (ELISA). There was a significant negative correlation between IL-1β and IL-12 levels and lesion size and disease duration, while IL-37 and IL-35 levels were significantly positively correlated with both lesion size and disease duration. The analysis of the risk factors of higher circulatory levels of IL-37 in patients of mycetoma showed a negative significant association with IL-1β cytokine, where a unit increment in IL-1β will decrease the levels of IL-37 by 35.28 pg/ml. The levels of IL-37 among the patients with a duration of mycetoma infection ≤ 1 year were significantly low by an average of 18.45 pg/ml compared to patients with a mycetoma infection's duration of ≥ 5years (reference group). Furthermore, the risk factors of higher levels of IL-35 in mycetoma patients revealed a negative significant association with IL-12, as a unit increment in IL-12 decreases the levels of IL-35 by 8.99 pg/ml (p < 0.001). Levels of IL-35 among the patients with duration of mycetoma infection ≤ one year were significantly low on average by 41.82 pg/ml (p value = 0.002) compared to patients with a duration of mycetoma infection ≥ 5 years (reference group). In conclusion, this study indicates that both IL-35 and IL-37 are negatively associated with the levels of IL-1β and IL-12 in eumycetoma mycetoma infection; and high levels of IL-37 and IL-35 may have a negative impact on disease progression.

Dataset Information

Bayesian modeling suggests that IL-12 (p40), IL-13 and MCP-1 drive murine cytokine networks in vivo.

Publications

Bayesian modeling suggests that IL-12 (p40), IL-13 and MCP-1 drive murine cytokine networks in vivo.

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