Cytokine Network Involvement in Subjects Exposed to Benzene

Table 1

Summary of considered studies on hematotoxicity induced by benzene and/or its metabolites.

Cytokine involved	Substance(s)	Effect(s)	Reference
TNF-α	Benzene	Similar peripheral levels in exposed subjects and controls	Rothman et al., 1996 [28]
	HQ	Dose-dependent inhibition of TNF-α-induced activation of NF-kB	Kerzic et al., 2003 [26]
		Synergistic action of hydroquinone and TNF-α in producing apoptosis in human bone marrow cells.	Kerzic et al., 2003 [26]
	Benzene	−238 (G→A) polymorphism is associated with the development of persistent bone marrow dysplasia developing in patients previously exposed to benzene	Lv et al., 2007 [27]
	HQ, benzenetriol, BQ, and catechol	Dose-dependent increase in TNF-α production by activated PBMC	Gillis et al., 2007 [21]
	BTX	Dose-dependent reduction in TNF production by PBMC	Haro-García et al., 2012 [29]
IL-1	HQ	Prevention of the proteolytic conversion of pre-IL-lα to the mature cytokine by the processing protease calpain	Renz and Kalf, 1991 [22]
	HQ	Dose-dependent reduction of IL-1α and IL-1β by mononuclear phagocytes	Carbonnelle et al., 1995 [23]
	HQ	Inhibition of pre-interleukin-lβ production by interleukin-lβ convertase	Niculescu et al., 1995 [24]
	HQ, catechol	Suppression of IL-1β production by activated PBMC	Gillis et al., 2007 [21]
	Benzene	−889 (C > T) polymorphism is associated with the decrease of granulocyte count	Lan et al., 2005 [19]
IL-2	BQ	Decrease in IL-2 production by activated PBMC	Gillis et al., 2007 [21]
IL-3	Benzene	Nondetectable peripheral levels	Rothman et al., 1996 [28]
IL-4	Benzene	−1098 (T > G) polymorphism is associated with decreased granulocyte and total lymphocytes counts	Lan et al., 2005 [19]
IL-6	Benzene	Similar peripheral levels in exposed subjects and controls	Rothman et al., 1996 [28]
	Benzenetriol, BQ, and catechol	Increased IL-6 production by activated PBMC	Gillis et al., 2007 [21]
IL-10	Benzene	No statistically significant difference in peripheral levels of exposed subjects and controls	Spatari et al., 2013 [30]
	BMX	No statistically significant dose-dependent reduction in IL-10 production by PBMC	Haro-García et al., 2012 [29]
	HQ, catechol	Strong inhibition of IL-10 production by activated PBMC	Gillis et al., 2007 [21]
	Benzene	−819 (T > C) polymorphism is associated with the decrease of granulocyte count	Lan et al., 2005 [19]
IL-12	BMX	No statistically significant dose-dependent reduction in IL-10 production by PBMC	Haro-García et al., 2012 [29]
	Benzene	−8685 (G > A) polymorphism is associated with decreased granulocytes, total lymphocyte count, and CD4^+ and CD8^+ T-cell subsets.	Lan et al., 2005 [19]
IFN-γ	HQ	Increased IFN-γ production by activated PBMC	Gillis et al., 2007 [21]
VCAM1	Benzene	−1591 (T > C) polymorphism is associated with decreased B cells, natural killer cells, CD4^+ T cells, and monocytes and colony-forming unit granulocyte-erythroid-macrophage-megakaryocyte progenitor cells	Lan et al., 2005 [19]
PF4	Benzene	Downregulation of the expression	Vermeulen et al., 2005 [31]
CTAP-III	Benzene	Downregulation of the expression	Vermeulen et al., 2005 [31]
CXCL12	BQ; HQ	Upregulation of gene expression; Downregulation of gene expression	Zolghadr et al., 2012 [34]
IL-8	HQ, catechol	Increased IL-8 production by PBMC; Decreased IL-8 production by activated PBMC	Gillis et al., 2007 [21]
	Benzenetriol, BQ	Increased IL-8 production by PBMC
Eotaxin, MIP1-α, and RANTES	HQ, benzenetriol, BQ, and catechol	Increased chemokines production by PBMC	Gillis et al., 2007 [21]
MCP-1	HQ, benzenetriol, and BQ	Increased MCP-1 production by PBMC	Gillis et al., 2007 [21]
	HQ, catechol	Decreased IL-8 production by activated PBMC	Gillis et al., 2007 [21]

HQ: hydroquinone; BQ: benzoquinone; BTX: benzene-toluene-xylene mixture; PBMC: peripheral blood mononuclear cells; PF4: platelet factor 4; CTAP-III: connective tissue activating peptide; CXCL: CXC chemokine ligand.