The relation of aggression, hostility, and anger to lipopolysaccharide-stimulated tumor necrosis factor (TNF)-α by blood monocytes from normal men
Introduction
Aggression, hostility, and anger (AHA) are independently associated with the development and progression of atherosclerotic cardiovascular disease (ACVD; Matsumoto et al., 1993; Siegman & Smith, 1992; Williams et al., 2000). At this time, it is not well understood how AHA influences ACVD. It has been proposed that the link between ACVD and AHA involves the relation of AHA to behavioral factors, such as increased smoking (Scherwitz & Rugulies, 1992), and physiological mechanisms, such as increased lipids and excessive cardiovascular and neuroendocrine responses to stress (see Siegman & Smith, 1992 for review), that contribute to the atherosclerotic process. However, the current understanding of atherosclerosis emphasizes a response to endo-thelial injury involving inflammatory cells, such as monocytes and T-cells, and the production of various atherogenic cytokines (Ross, 1999). It is thought that inflammation not only characterizes atherogenesis but also contributes to the progression of atherosclerosis (Ross, 1993, 1999). Previous studies have linked hostility and anger to mitogenic responses and number of natural killer (NK) and B-cells (Christensen et al., 1996; Miller, Dopp, Myers, Stevens, & Fahey, 1999; Mills, Dimsdale, Nelesen, & Dillon, 1996), but these cells and their corresponding activities have not been directly implicated in the pathogenesis of ACVD (Schwartz, Valente, & Sprague, 1993). Although other psychosocial risk factors of ACVD, such as major depression, have been linked with increased cytokine expression (Maes, 1999), at this time it is not known whether AHA are associated with inflammatory cellular activities and proinflammatory molecules involved in the pathogenesis of ACVD.
An important proinflammatory cytokine that has been implicated in the pathogenesis of cardiovascular disease is tumor necrosis factor (TNF)-α (Ferrari, 1999). TNF-α is a molecule primarily produced by activated monocytes and macrophages (Vasalli, 1992). TNF-α is released in all stages of the inflammatory process associated with atherogenesis (Ross, 1999; Schwartz et al., 1993). A number of studies have shown that TNF-cx has profound effects on altering endothelial cell function (Langler, Friers, & van Hinsberg, 1991) and promoting the expression of adhesion molecules on endothelial cells that contribute to cellular accumulation at the site of injury (Ikuta, Kirby, Shenton, Givan, & Lennard, 1991). TNF-α triggers the induction of interleukin (IL)-6 (Pang, Gouch, Batey, Clancy, & Cripps, 1994), a multifunctional cytokine that not only plays a central role in inflammation but also predicts future coronary events in initially healthy men (Ridker, Rifai, Stampler, & Hennekens, 2000). TNF-α also promotes the production of acute phase proteins such as C-reactive protein (Richards & Gauldie, 1995), another inflammatory risk factor for cardiovascular disease (Danesh, Collins, Appleby, & Peto, 1998). Not surprisingly, TNF-α production by macrophages is increased in atherosclerotic vessels (Barath et al., 1990), in patients with ACVD (Basaran et al., 1993; Vaddi, Nicoloni, Mehta, & Mehta, 1994), and in asymptomatic individuals with traditional risk factors (Elneihoum, Falke, Helblad, Lindgarde, & Ohlsson, 1997; Mendall et al., 1997). Recently, TNF-α production has also been linked to two well-recognized psychosocial risk factors of ACVD. Relative to individuals living in rural farming areas in India, urban slum dwellers, and middle class urbanites, known to be at an increased risk of ACVD, exhibited higher TNF-α levels (Yudkin, Yajnik, Mohamed-Ali, & Bulmer, 1999). Similarly, major depression has also been linked with TNF-α such that depressed individuals show higher concentrations and greater expression of TNF-α (Maes, 1999). Although preliminary, these latter findings underscore the possibility that other recognized psychosocial risk factors of ACVD, such as AHA, are associated with TNF-α.
The purpose of the current study was to examine the relation of AHA to monocyte-associated TNF-α expression following stimulation by lipopolysaccharide (LPS, Salmonella, Sigma Chemical, St. Louis, MO). Given previous observations, we hypothesized a priori that AHA would be associated with heightened expression of monocyte-associated TNF-α following LPS stimulation.
Section snippets
Methods
Subjects. Participants were 62 healthy, nonsmoking men (ages 18–45 years) in the Raleigh–Durham–Chapel Hill area recruited via advertisements placed in local newspapers and fliers placed throughout the community. Interested individuals were told that the purpose of the study was to examine the relation of various psychological factors to health promotion and disease prevention without identifying which diseases or psychological factors were the focus of the study. Therefore, participants were
Results
Table 1 presents mean and SDs for age and BPAQ scores and distribution for race, alcohol use, and educational status. For the most part, participants were well educated and a minority (22%) of subjects reported regular alcohol consumption. Given the distribution of subjects across race, educational status and alcohol use, we collapsed cells among each of these categories. For race, we compared whites to minorities. For educational status, we grouped individuals with college degrees or more
Discussion
We hypothesized that aggression, hostility, and anger would be associated with an enhanced LPS-stimulated expression of monocyte-associated TNF-α in healthy, non-smoking men. Results of this study were supportive of our hypothesis. Univariate analyses indicated a significant positive correlation between TNF-α expression and aggression, assessed via the BPAQ. Furthermore, results of multivariate regression indicated that aggression significantly predicted LPS-stimulated TNF-α expression even
Acknowledgments
This work was supported by a National Heart, Lung, and Blood Institute grant (Grant HL56105 to E.C.S.). The authors thank Karen Achanzar, Kenneth Young, and the Comprehensive Cancer Center Flow Cytometry Facility, under the direction of Michael J. Cook, Ph.D., for conducting the flow cytometry analyses. Lastly, we wish to thank Melanie Tirronen, Sarah Rush, and Tara Pennington for data collection.
References (48)
- et al.
Detection and localization of tumor necrosis factor in human atheroma
Am. J. Cardiol.
(1990) - et al.
Leukocyte activation in atherosclerosis: correlation with risk factors
Atherosclerosis
(1997) The role of TNF in cardiovascular disease
Pharmacol Res.
(1999)- et al.
Temporal regulation by adrenergic receptor stimulation of macrophage (M phi)-derived tumor necrosis factor (TNF) production post-LPS challenge
Neuroimmunology
(1996) - et al.
The effects of psychological stress on humans: increased production of pro-inflammatory cytokines and a TH-1-like response in stress-induced anxiety
Cytokines
(1998) - et al.
Psychologic characteristics associated with acute stressor-induced leukocyte subset redistribution
J. Psychosom. Res.
(1996) - et al.
Alteration of intracellular traffic by monensin; mechanism, specificity, and relationship to toxicity
Biochim. Biophys. Acta
(1990) - et al.
Enhancement of serotonin transporter function by tumor necrosis factor alpha but not interleukin-6
Neurochem. Int.
(1998) - et al.
Hostility and adrenergic receptor responsiveness: evidence for reduced b-receptor responsiveness in high hostile men
J. Psychosom. Med.
(1998) - et al.
Serotonin inhibition of tumor necrosis factor-α synthesis by human monocytes
Life Sci.
(1991)
Serum tumor necrosis factor levels in acute myocardial infarction and unstable angina
Angiology
Aging, tumor necrosis factor-alpha (TNF-α) and atherosclerosis
Clin. Exp. Immunol.
An inventory for assessing different kinds of hostility
J. Consult. Psychol.
The aggression questionnaire
J. Pers. Soc. Psychol.
Effect of verbal self-disclosure on natural killer cell activity: moderating effect of cynical hostility
Psychosom. Med.
Central serotonin activity and aggression: Inverse relationship with prolactin response to d-fenfluramine, but not with CSF 5-HIAA concentration in human subjects
Am. J. Psychiatry
Association of fibrinogen, C-reactive protein, albumin, and leukocyte count with coronary heart disease: meta-analyses of prospective studies
J. Am. Med. Assoc.
Construct validation of health-relevant personality traits: interpersonal circumplex and five-factor model analyses of the aggression questionnaire
Int. J. Behav. Med.
Human endothelial cells: effect of TNF-α on peripheral blood mononuclear cell adhesion
Immunology
Effects of tumor necrosis factor on prostacyclin production and the barrier function of human endothelial cell monolayer
Arterioscler. Thromb.
Macrophage-induced angiogenesis is mediated by tumor necrosis factor
Nature
Phagocyte function in familial hypercholesterolaemia: peripheral blood monocytes exposed to lipopolysaccharide show increased tumor necrosis factor production
Scand. J. Immunol.
Major depression and activation of the inflammatory response system
Adv. Exp. Med. Biol.
Aggression, impulsivity, and central nervous system serotonergic responsivity in a nonpatient sample
Neuropsychopharmacology
Cited by (113)
The association between social class and aggression: A meta-analytic review
2024, Social Science and MedicineImpulsive and aggressive traits and increased peripheral inflammatory status as psychobiological substrates of homicide behavior in schizophrenia
2022, European Journal of PsychiatryCitation Excerpt :Inflammation can have a complex central neuromodulatory role in the occurrence of aggression in humans through its effects on neurotransmitters. Additionally, increased levels of circulating proinflammatory mediators such as tumor necrosis factor (TNF)-α and C-reactive protein (CRP) were shown to be associated with aggression, hostility, and anger in healthy individuals.13,14 Although peripheral indicators of inflammation have been suggested to reflect both the pathogenesis and behavioral phenotype in schizophrenia, the facilitatory role of immuno-inflammatory mechanisms in aggressive and violent behavior in schizophrenia is yet to be understood.15,16
Identification and expression pattern of the sex determination gene fruitless-like in Cherax quadricarinatus
2022, Comparative Biochemistry and Physiology Part - B: Biochemistry and Molecular BiologyCitation Excerpt :Aggressive behavior is common among C. quadricarinatus and causes a large number of deaths. Many studies have indicated a role for TNF signaling in modulating aggressive behavior (Suarez et al., 2002; Bhatt et al., 2009; Patel et al., 2010). In this study, RNAi was used to explore the effect of the expression level of Cq-TNF by silencing the Cqfru gene in C. quadricarinatus.
Relationships between inflammatory markers and suicide risk status in major depression
2021, Journal of Psychiatric Research