Table 1.

Summary of studies on inflammatory response to vaccination.

Vaccination	Year	Studies	Number of subjects	Markers	Type of sample	Time course	Level observed	Results
DTwP/DTaP, Hib, HBV, IPV	1998	[19]	89 preterm infants	IL-6, CRP	Serum	0, 12, 36, 48 hours after injection	IL-6 (130 pg/mL) CRP (4.0 mg/dL)	IL-6: responded at the peak level at 12 hours after vaccination CRP: peak level at 36 hours after vaccination of DTwP but not DTaP, respectively
DT-Polio-Typhim	2005	[69]	7 elderly; 8 young adults	CRP, fibrinogen, albumin, α1-acid glycoprotein (AGP), al-antitrypsin, transthyretin and transferrin	Plasma	7 days before vaccination and 2 days after injection	CRP in elderly (7.1 mg/L); in young adults (11.5 mg/L)	CRP and AGP levels increased after 2 days after vaccination, (p < 0.05); no significant change in other acute-phase proteins
Hepatitis B	2013	[18]	70 infants	IL-6, CRP	Plasma	0 and 24 hours after injection	CRP (3.8 mg/L) IL-6 (11.4 pg/mL)	IL-6: no change (p > 0.05) CRP: level increased after 24 h (p < 0.001)
Salmonella typhi	2000	[70]	18 adults	Body temperature, IL-1β, IL-1Ra, IL-6, TNFα	Serum	0, 1, 2, 3, 4, 5, 6, 7, 8, and 32 hours after injection	IL-6 (5.8 pg/mL) IL-1Ra (593.6 pg/mL)	No change in body temperature; no change in IL-1β and TNFα; IL-1Ra level increased peak at 3 hours afterwards vaccination (p < 0.05); IL-6 level increased within 8 hours after vaccination (p = 0.07)
	2002	[71]	17 adults	CRP, IL-6, IL-1Ra, TNF-α	Plasma	0, 1, 2, 3, 4, 5, 6, 7, and 8 hours after injection	Not indicated	CRP: No significant changes within 8 hours after vaccination TNF-α: Level increased at 4 hours after vaccination IL-6: Level increased gradually for the first 4 hours and peaking at 4 hours after vaccination
	2005	[72]	30 male adults	IL-1Ra, IL6, TNF-α	Plasma	0, 3, and 6 hours after injection	IL-6 (1.59 pg/mL) IL-1Ra (682.92 pg/mL) TNF-α (248 pg/mL)	IL-6: level increased after 3 h IL-1Ra & TNF-α: No significant changes
	2013	[20]	8 male adults	CRP, IL-6, TNF-α	Plasma	0, 4, 5, 6, 7, 8, and 24 hours after injection	CRP (<0.1 mg/L) IL-6 (<6 pg/mL) TNF-α (<8 pg/mL)	IL6: peak at 6-7 h (p < 0.05) TNF-α: peak at 6–8 h (p = 0.034) CRP: level not increase within first 8 hours, perhaps peak after 24 h (p = 0.027)
Influenza	2005	[73]	22 adults	CRP, IL-6, MCP-1, TNF-α, IL-2sRα, and serum amyloid A (SAA)	Plasma	0, 1, 3, and 7 days after injection	Influenza CRP (1.4 mg/L) IL-6 (1.9 pg/mL)	CRP: level increased at day-1 (p < 0.01) and day-3 (p = 0.05) after vaccination IL-6: level increased peaking at day-1 after vaccination SAA: level increased at day-1 (p < 0.05) TNF-α and IL-2sRα: Not significant changes
	2011	[23]	46 pregnant women	CRP, IL-6, TNF-α	Serum	0, 1, 2, and 7 days after injection	CRP (0.85 mg/L) IL-6 (0.2 pg/mL) TNF-α (0.65 pg/mL)	CRP: level increased one and two days after vaccination (p < 0.05) TNF-α: level increased 2 days after vaccination (p = 0.06) IL-6: No significant change
	2013	[74]	28 pregnant & 28 nonpregnant women	IL-6, TNF-α, IL-1β, IL-8, MIF	Serum	0, 1, 2, and 3 days after injection	IL-6 (approx. 1.5 pg/mL) TNF-α (approx. 15.8 pg/mL) Il-1β (approx. 0.7 pg/mL) IL-8 (approx. 6–8 pg/mL) MIF (approx. 10 pg/mL)	TNF-α and IL-6: Level increased, peaking at one day after vaccination (p < 0.001); IL-1β and MIF: no significant change; IL-8: Level decreased in nonpregnant women; no change in pregnant women
Influenza; influenza + pneumococcal	2004	[22]	39 adults	CRP	Plasma	0, 2, or 3 days or 4 or 5 days after injection	Influenza CRP (2.7 mg/L) Influenza + pneumococcal CRP (3.7 mg/L)	CRP: level increased and peak at day 2 after vaccination
17D yellow fever	2002	[21]	10 adults	IL-6, CRP, fibrinogen	Plasma	0, 1, 2, 3, 4, 5, 6, 7, and 8 days after injection	IL-6 (0.33 pg/mL) CRP (1.20 ng/mL) Fibrinogen (2.91 g/L)	IL-6: level increased 30% on days 5 & 6 after injection (p < 0.05) CRP: level increased 45% on days 6 & 7 (p < 0.05) Fibrinogen: level increased 10% on day 2 and further arise on day 5 onwards (p < 0.05)