Social Support, Relationships, and Health: A Psychoneuroimmunological Review

Abstract

Social support and interpersonal relationships represent foundational determinants of human health, operating 
through complex psychoneuroimmunological (PNI) mechanisms that bridge psychological experience with 
biological function. This review examines the extant literature on the interrelationships among social support, 
relational quality, and health outcomes from a psychoneuroimmunological perspective, synthesizing evidence 
from over 150 empirical and review studies published between 1977 and 2024. We interrogate the pathways 
through which perceived and received social support modulate neuroendocrine, autonomic, and immune 
functioning, with particular attention to hypothalamic-pituitary-adrenal (HPA) axis dysregulation, sympathetic 
nervous system activation, inflammatory cytokine profiles, and natural killer cell activity. Meta-analytic findings 
consistently demonstrate that social isolation and low perceived support are associated with elevated cortisol, 
heightened interleukin-6 (IL-6) and C-reactive protein (CRP), and suppressed lymphocyte proliferation. 
Conversely, high-quality close relationships buffer allostatic load, attenuate inflammatory responses, and confer 
significant protective effects against cardiovascular disease, cancer progression, infectious illness, and all-cause 
mortality. Theoretical frameworks including the stress-buffering hypothesis, the direct effects model, and the 
social regulation of biology model are critically evaluated for their explanatory utility. The review highlights 
critical methodological considerations, identifies gaps in the literature pertaining to bidirectionality and 
mechanism specificity, and proposes directions for future longitudinal and intervention research. The synthesis 
underscores social connectedness as a fundamental biological need, with implications for clinical practice, public 
health policy, and the design of behavioral interventions across the lifespan.