Interleukins and interleukin receptors in rheumatoid arthritis: Research, diagnostics and clinical implications

Table 1 Characteristics of cytokines in rheumatoid arthritis

Family	Cytokine	Cytogenetic location	Molecular weight	Receptor	Cell source
IL-1	IL-1B	2q14	17 kD	IL-1R1	Macrophages, monocytes, lymphocytes, keratinocytes, microglia, megakaryocytes, neutrophils, fibroblasts and synovial lining cells
	(IL-1F2)			IL-1R2
	IL-1RN	2q14.2	16.1-20 kD	IL-1R1	Monocytes, macrophages, fibroblasts, neutrophils, epithelial cells and keratinocytes
	(IL-1F3)			IL-1R2
	IL-18	11q22.2-q22.3	22.3 kD	IL-18R1	Macrophages, Kupffer cells, keratinocytes, osteoblasts, astrocytes, and DCs
	(IL-1F4)			IL-18RAP
IL-2	IL-2	4q26-q27	15.5 kD	IL-2R	CD4+, CD8+ activated T cells, DCs, NK and NKT cells
	IL-2RA	10p15-p14	30.8 kD	IL-2R	Activated T and B cells, thymocytes, myeloid precursors and olygodendrocytes
	IL-4	5q23-q31	15 kD	IL-4R1	Th2 cells, basophils, eosinophils, mast cells, NKT and γ/δ T cells
				IL-4R2
	IL-15	4q31	14-15 kD	IL-15R	Monocytes, activated CD4+ T cells, keratinocytes, skeletal muscle cells
	IL-21	4q26-q27	15 kD	IL-21R	T and NKT cells
IL-10	IL-10	1q31-q32	18.6 kD	IL-10RA/IL-10RB	T and B cells, monocytes, macrophages and DCs
IL-12	IL-23	12q13.13	19 kD	IL-12RB1/IL-23R	Macrophages and activated DCs
IL-6-like cytokines	IL-6	7p21-p15	19-26 kD	IL-6R/IL-6ST	Endothelial cells, fibroblasts, monocytes/ macrophages
IL-17	IL-17A	6p12	35 kD	IL-17RA/IL-17RC	Th17, CD8+ T cells, NK cells, NKT cells, γ/δ T cells and neutrophils
	IL-17F	6p12	44 kD	IL-17RA/IL-17RC	Th17, CD8+ T cells, NK cells, NKT cells, γ/δ T ells and neutrophils
Chemokines	IL-8	4q13-q21	16 kD	IL-8RA/IL-8RB	Monocytes, macrophages, neutrophils, lymphocytes, endothelial cells, epithelial cells, fibroblasts, keratinocytes, chondrocytes, synovial cells, and hepatocytes

NK: Natural killer cells, NKT: Natural killer T cells, DCs: Dendritic cells; IL: Interleukin.

Table 2 The examined interleukin and interleukin receptor gene polymorphisms that are associated with rheumatoid arthritis

Gene	Polymorphism	Population	Ref.
IL-1B	rs16944	Algerian, British, Turkish	[34,35,40]
	rs1143623	British	[35]
	rs1143634	Algerian, Asian, Turkish	[34,40-42]
IL1-RN	rs419598	Black South Africans	[36]
IL-2/IL-21	rs907715	Australasian	[72]
	rs6822844	Australasian, Dutch	[65,72]
	rs17388568	Australasian	[72]
IL-2RA	rs2104286	Dutch	[64]
IL-4	rs2243250	Egyptian, Polish	[51,52]
IL-4R	rs1801275	African American, Egyptian	[54,55]
	rs1805010	African American, Egyptian	[54,55]
IL-6	rs1800795	Iranian, United Kingdom, Spain, Spanish, Turkish	[34,114,116, 117,122]
	rs1800796	Han Chinese, Taiwan, Turkish	[34,43,47,118]
IL-8	rs112664	Taiwan	[118]
	rs2227306	Caucasian	[137]
IL-10	rs1800871	Malaysian, Polish	[80,81]
	rs1800872	Chinese, Malaysian, Polish	[80-82]
	rs1800896	Malaysian, Polish	[80,81]
IL-15	rs2322182	North European	[59]
	rs4371699	North European	[59]
	rs6821171	North European	[59]
	rs7665842	North European	[59]
	rs7667746	North European	[59]
IL-17A	rs1974226	Japanese	[136]
	rs2275913	Norwegian	[135]
	rs3748067	Japanese	[136]
	rs3804513	Japanese	[136]
IL-17F	rs763780	Polish	[134]
	rs2397084	Polish	[134]
IL-18	rs187238	Chinese, Egyptian	[46,47]
	rs549908	Taiwan	[48]
	rs360718	Japanese	[49]
	rs360722	Japanese	[49]
	rs1946518	Chinese, Egyptian, Japanese	[46,47,49]
IL-23R	rs1004819	European, New Zealand, Spanish	[97,100,106]
	rs1343151	European, New Zealand, Spanish	[97,100,106]
	rs1495965	Spanish	[97]
	rs2201841	European, New Zealand, Hungarian	[96,97,100,106]
	rs7517847	European, New Zealand, Spanish	[97,100,106]
	rs7530511	Caucasian	[98]
	rs10889677	Hungarian	[96]
	rs11209026	European, Caucasian, New Zealand	[98,100,106]
	rs11209032	Spanish	[97]
	rs10489629	Europan, New Zealand, Spanish	[97,100,106]