# Cytokines Physiology > Cytokines in MBBS Physiology: interleukin functions, TNF, interferons, TH1 and TH2 profiles, fever and acute phase mechanisms and biological drug targets. - Canonical URL: https://prepelephant.com/topics/mbbs/physiology/cytokines-physiology - Exam / course: MBBS · Subject: Physiology - Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team - First published: 2026-10-02 - Last updated: 2026-10-02 - How to cite: "Cytokines Physiology", PrepElephant, https://prepelephant.com/topics/mbbs/physiology/cytokines-physiology ## Direct answer Cytokines are low-molecular-weight glycoprotein messengers — interleukins, interferons, tumour necrosis factors, colony-stimulating factors and chemokines — acting at picomolar to nanomolar concentrations through receptors linked to JAK-STAT and NF-kappaB pathways, most often autocrine or paracrine, and behaving pleiotropically (one cytokine, many actions) and redundantly (many cytokines, one action). The examinable anchors: IL-1 and TNF-alpha are the endogenous pyrogens driving fever through prostaglandin E2 in the hypothalamus and the acute-phase response; IL-2 grows T cells; IL-6 induces C-reactive protein; IL-4 switches B cells to IgE; IL-5 drives eosinophils; IL-12 commits TH1 cells; IL-17 organises neutrophilic inflammation; IL-10 is the chief anti-inflammatory brake. ## What you must remember - **Fever mechanism:** IL-1, TNF-alpha and IL-6 reach the organum vasculosum of the lamina terminalis, induce cyclo-oxygenase-2 and PGE2, and raise the hypothalamic set point — paracetamol works by blocking this step, not by cooling. - **Acute-phase response:** IL-6 (with IL-1 and TNF) drives hepatocytes to make CRP (rising up to hundreds of fold within 24-48 hours), fibrinogen (the ESR story), serum amyloid A, while albumin falls — the laboratory face of inflammation. - **T-helper mapping:** TH1 — IL-12 and IFN-gamma for intracellular organisms; TH2 — IL-4, IL-5, IL-13 for helminths and allergy; TH17 — IL-6 plus TGF-beta with IL-23 maintenance, for extracellular bacteria and autoimmunity. - **Allergy pair:** IL-4 provides the IgE class switch and IL-5 the eosinophil arm — together they write the pathology of asthma and parasitic defence. - **Natural anti-inflammatory:** IL-10 (from regulatory T cells and macrophages) shuts off macrophage cytokine output; IL-1 receptor antagonist (anakinra) is its drug-shelf cousin. - **Chemokine flagship:** IL-8 (CXCL8), the neutrophil chemotaxin attracting the first wave to any bacterial focus. - **Interferons:** type I (alpha and beta) establish the antiviral state in neighbouring cells; type II (IFN-gamma) activates macrophages — the macrophage's whistle for mycobacteria, deficient in its receptor pathway in children with disseminated BCG. - **Clinical arms of the network:** TNF-alpha — septic shock, cachexia (anti-TNF: infliximab, etanercept); IL-6 — tocilizumab in rheumatoid arthritis and cytokine-release syndrome; IL-17 — secukinumab in psoriasis; IL-12/23 p40 — ustekinumab; G-CSF — filgrastim to rescue chemotherapy neutropenia. - **Cytokine storm:** the runaway amplification seen in CAR-T therapy (IL-6-dominated, tocilizumab-responsive), haemophagocytic lymphohistiocytosis and severe sepsis — the same molecules that coordinate defence becoming lethal in excess. ## A worked case: fever after CAR-T infusion Three days after chimeric antigen receptor T-cell infusion for leukaemia, a young adult spikes a fever of 39.5°C with hypotension and a CRP and ferritin climbing steeply. Activated T cells and monocytes have flooded the circulation with IL-6, TNF-alpha and IL-1 — the textbook cytokine storm, graded clinically rather than by any single level. The physiology picks the drug: the IL-6 axis dominates CAR-T release syndrome, so the IL-6 receptor antibody tocilizumab is first-line (steroids are added for higher grades, a mirror image of sepsis where steroids are last-resort). Fever here is not the enemy — it is PGE2-mediated set-point elevation by IL-1 and IL-6, and the treating team's priority is the vascular leak and macrophage activation behind it, not the temperature on the chart. ## How the exam frames it Match-the-following questions on the interleukins are near-guaranteed. The recurring quartet: IL-1 (endogenous pyrogen, also called lymphocyte-activating factor historically), IL-2 (T-cell growth — and the therapeutic target of basiliximab in transplantation and the agent itself in renal cell carcinoma), IL-6 (CRP and B-cell differentiation), IL-4 (IgE). Two conceptual follow-ups separate ranks: why single-cytokine redundancy matters (knockouts are often mild because of overlap — but the fever mechanism has no redundant bypass for PGE2), and which cytokine is measured clinically (CRP as IL-6's surrogate — nobody orders an IL-6 in a district hospital). ## Frequently asked questions ### Which cytokines cause fever and by what mechanism? IL-1, TNF-alpha and IL-6 act as endogenous pyrogens, inducing PGE2 in the OVLT region of the hypothalamus to raise the set point — the step paracetamol blocks. ### Which cytokine drives C-reactive protein synthesis? Interleukin-6, acting on hepatocytes; CRP can rise several hundred-fold within 48 hours and is the standard clinical surrogate of the IL-6 axis. ### Which cytokines characterise TH1 and TH2 responses? TH1 cells produce IFN-gamma (with IL-12 as their inducer) for intracellular pathogens; TH2 cells produce IL-4, IL-5 and IL-13 for helminths and allergic IgE responses. ### What is the role of IL-17 in disease? Produced by TH17 cells, it recruits neutrophils via chemokines and antimicrobial peptides; overactivity drives psoriasis, ankylosing spondylitis and other autoinflammatory patterns — the target of secukinumab. ### What is cytokine release syndrome and its first-line drug? A runaway IL-6- and TNF-dominated inflammatory syndrome after CAR-T therapy (and in HLH or severe sepsis), treated first-line in CAR-T cases with the IL-6 receptor antibody tocilizumab.