Cytokines, once known as ‘lymphokines’, are low molecular-weight signaling molecules released in response to a variety of stimuli in physiological and pathological conditions. Cytokines stem from physically or biochemically stressed tissues and circulating immune cells. They exert both local and systemic effects and participate in a broad-spectrum of immunobiological mechanisms, modulating host inflammatory response. Cytokines are crucial in maintaining barrier integrity between body surfaces and cavities. They also help to furnish immune privilege in critical compartments like the central nervous system and the testes, interacting with leukocyte trafficking to and from inflammatory sites. They act on mechanisms that unleash and recruit effector cells to eliminate tissue-dwelling microorganisms that threaten homeostasis. The concurrence and stay of inflammatory cells are determined by the locoregional immune landscape, provided by the dominating cytokine networks. Through interactions with endothelial monolayers in blood and lymphatic vasculature, locally produced cytokines exert paracrine effects on the residence time of incoming cells. Cytokines affect vascular permeability, tissue drainage, and immune-cell migration, resulting in clonal expansion and differentiation and contributing to immunological memory. Blood-borne cytokines may give rise to acute-phase proteins with specialized functions. Crosstalk with thrombosis and fibrinolytic pathways may start immunothrombosis and tissue repair programs to restore homeostasis. Cytokines affect temperature regulation, neurotransmitter trafficking, and host behavior upon passing the blood-brain barrier, among other central effects.

At the cellular level, cytokines trigger a wide array of molecular programs in responding cells where the outcome depends on cell type, expression of the cognate receptor, signaling transduction, cell cycle/differentiation, microenvironment, cytokine availability, and other determinants. Today, the classical dichotomy classifying cytokines in pro-and anti-inflammatory categories has evolved to the conceptual view of a spectrum of immunological signals that are spatiotemporal- and context-dependent. Cytokines are central orchestrators of the chronic inflammatory state in clinical conditions including metabolic syndrome, diabetes, neuro-inflammation, cancer, asthma, and auto-immune diseases. Their impact on clinical outcomes has been corroborated by many interventional trials. The growing number of new drugs targeting disease-associated cytokines has led to a breakthrough in treatment strategies in life-threatening diseases. Current limitations encompass our failure to discriminate high-ranking members from bystanders in the hierarchy of cytokines throughout the chronic inflammatory state in individual patients.

This Special Issue aims to collate the emerging evidence on cytokine functions in clinical settings where the immune system is detected, to unravel their pathophysiological role, and empower cytokine-targeting strategies in a broad spectrum of auto-immune and auto-inflammatory conditions. Original research and review articles are welcome.

Potential topics include but are not limited to the following:

• Cytokines and autoimmunity: an updated overview
• IL-17-driven rheumatic disorders
• Cytokine and autoimmune thyroid pathology
• Cytokines and herpetiform dermatitis
• Cytokines and autoimmune blistering skin diseases
• Cytokines and transplantation and autoimmunity
• Cytokines and dysmetabolism in systemic autoimmune diseases
• Adipokines, metabolic syndrome, and rheumatic diseases
• Cytokines and immunomediated neurological disease
• Systemic lateral sclerosis and cytokines
• Anti-cytokine therapy in autoimmune diseases like rheumatoid arthritis
• Cytokines in neurodegeneration and neuroprotection
• IL-1 and in vivo neurodegeneration
• Cytokines upon activation of astrocytes and microglia in inflammation
• Neuronal apoptosis induced by increased production of IL-1 and TNF-α