C-C motif chemokine 4 (CCL4) (CCL4)

C-C motif chemokine 4 (CCL4), commonly known as macrophage inflammatory protein 1-beta (MIP-1β), is a small secreted cytokine from the CC chemokine family produced by activated macrophages, lymphocytes, and other immune cells at inflammation sites. It functions primarily as a chemoattractant for monocytes, natural killer cells, T cells, and granulocytes (neutrophils, eosinophils, basophils), driving inflammatory and immune responses including cell migration, activation, and synergy with IFN-γ to enhance macrophage production of IL-12 and TNF-α. CCL4 binds G-protein-coupled receptors CCR5 (primary) and CCR1, down-modulating CCR5 to inhibit HIV-1 entry into T cells, positioning it as a natural antiviral factor. In disease, it contributes to acute inflammation, infections like listeriosis, bone resorption, and tumor microenvironments in cancers such as breast carcinoma by regulating monocyte cytotoxicity and cytokine release. Although not directly targeted by approved drugs, its receptors (e.g., CCR5) are modulated by HIV entry inhibitors like maraviroc, highlighting therapeutic potential in inflammation and infection but with risks of disrupting balanced immunity.

Other names

Macrophage inflammatory protein 1-betaMIP-1βMIP1bsmall inducible cytokine A4SCYA4lymphocyte activation gene 1 proteinLAG-1T-cell activation protein 2ACT-2secreted protein G-26

Binds CCR5 and CCR1 receptors to induce chemotaxis, down-modulate CCR5 surface expression, inhibit HIV entry; synergizes with IFN-γ for macrophage activation (IL-12, TNF-α production)