Interleukin

Interleukins (ILs) are a family of cytokines — protein signaling molecules — that mediate communication between cells of the immune system and between the immune system and the nervous system. First characterized in the 1970s as factors that stimulate leukocyte proliferation, interleukins are now recognized as central mediators of the neuro-immune axis, the bidirectional communication network linking immune function with neural processes.

Key members of the interleukin family include:

• IL-1β — a potent pro-inflammatory cytokine elevated during infection, tissue damage, and psychological stress. IL-1β crosses the blood-brain barrier and signals via the hypothalamus to induce fever, sickness behavior, and sleep. It is a primary mediator of sleep homeostasis and contributes to allostatic load when chronically elevated.

• IL-6 — a pleiotropic cytokine with both pro- and anti-inflammatory roles. Chronic elevation of IL-6 is associated with depression, cardiovascular disease, and cognitive decline. IL-6 levels rise during sleep deprivation and social stress, suggesting it is a molecular bridge between psychological experience and physiological dysregulation.

• IL-10 — an anti-inflammatory cytokine that helps resolve immune responses and prevent collateral tissue damage. Dysregulation of the IL-10 response is implicated in autoimmune disorders.

Interleukins signal through specific cell-surface receptors that activate intracellular pathways, most notably the JAK-STAT pathway and the NF-κB pathway. These pathways regulate gene expression for hundreds of target genes involved in inflammation, cell survival, and metabolism.

The cytokine theory of depression posits that major depressive disorder in some patients is not primarily a neurotransmitter imbalance but an inflammatory disorder mediated by elevated interleukins — particularly IL-1β and IL-6. This theory is supported by the observation that cytokine administration (e.g., interferon-alpha therapy for hepatitis C) induces depressive symptoms, and that anti-inflammatory treatments show antidepressant effects in subsets of patients.

Interleukins challenge the disciplinary boundary between neuroscience and immunology. They are not 'immune molecules with neural side effects.' They are evolutionarily conserved signaling systems that coordinate organism-wide responses to threat, injury, and stress.