Production of inflammatory cytokines in response to diphtheria-pertussis-tetanus (DPT), haemophilus influenzae type b (Hib), and 7-valent pneumococcal (PCV7) vaccines

Figures & data

Figure 1. IL-1β, IL-6, TNF-α, and G-CSF production in PBMCs cultures stimulated with DPT, Hib, PCV7, DPT/Hib, DPT/PCV7, Hib/PCV7, and DPT/Hib/PCV7. PBMCs were obtained from 29 individuals and culture fluids were harvested 24 h after stimulation. Cytokine concentrations were measured using BioPlex 17 cytokine panel. Each bar represents the mean concentration (•) with 95% CI.

Figure 2. IL-1β production in the PBMCs of 29 individuals. PBMCs were stimulated with DPT, Hib, PCV7, DPT/Hib, DPT/PCV7, Hib/PCV7, and DPT/Hib/PCV7. Columns from left to right in each individual show the production of IL-1β measured by EIA.

Table 1. Number of patients with or without febrile reactions after vaccination with a different combination of vaccines

Fever +			Fever –
DPT/Hib/PCV7	22		DPT/Hib/PCV7	4
DPT/Hib/PCV7/IPV	4		DPT/Hib/PCV7/Rota	1
DPT/Hib/PCV7/Rota	3
DPT/Hib/PCV7/BCG	1
PCV7/Hib	7		PCV7/Hib	6
PCV7/Hib/Rota	4		DPT/Hib	1
PCV7/DPT	1
PCV7	9		PCV7	4
PCV7/MR	3		DPT	2
Hib	3
PCV/Rota	1
PCV/IPV	1
PCV/IPV/Rota	1
PCV/Influenza	1
Total	61			18

DPT, Diphtheria, tetanus toxoids, combined with acellular pertussis vaccine; Hib, Hemophilus influenzae type b T-conjugated vaccine; PCV7, 7-valent pneumococcal conjugated vaccine; Rota, Rotavirus vaccine; BCG, Bacillus Calmette-Guérin; MR, Measles and rubella combined vaccine; IPV, Inactivated polio vaccine.

Figure 3. Cytokine profiles of 61 individuals with febrile reactions within 24 h after immunization (upper panel) and those of 18 recipients without febrile illness (lower panel).

Table 2. Cytokine profiles in vaccine recipients with or without febrile reactions

	Cytokine profile in subjects with febrile reaction after immunized with
	≥ 3 bacterial vaccines (n = 30)	2 bacterial vaccines (n = 12)	One bacterial vaccine (n = 19)
IL-1β	0.68 (0.36˜0.99)	0.78 (0.08˜1.48)	0.83 (-0.02˜1.67)
IL-4	0.41 (0.26˜0.56)	0.29 (0.11˜0.48)	0.35 (0.14˜0.57)
IL-6	29.44(17.35˜41.53)	12.53 (6.88˜18.20)	23.72 (11.53˜35.90)
IL-10	7.34 (1.97˜12.71)	3.6 (0.31˜6.88)	7.85 (3.04˜12.66)
IL-12	12.93 (-2.28˜28.15)	6.4 (-2.61˜13.07)	7.87 (1.27˜14.46)
G−CSF	87.24 (34.65˜139.83)	37.41 (18.99˜55.83)	39.88 (17.88˜61.88)
IFN-γ	49.95 (24.08˜75.09)	42.95 (3.58˜82.32)	33.26 (14.98˜51.54)
MIP-1β	66.81(41.33˜92.29)	59.97 (32.55˜87.38)	72.51 (27.10˜117.92)
TNF-α	13.43 (0.25˜26.62)	4.86 (1.94˜7.78)	11.3 (1.49˜21.11)
PGE2*	148.62 (90.7˜206.5))	114.36 (68.91˜159.8)	219.3 (51.49˜387.2)
	Cytokine profile in subjects without febrile illness after immunized with			Normal (n = 10)
	≥ 3 bacterial vaccines (n = 5)	2 bacterial vaccines (n = 7)	One bacterial vaccine (n = 6)
IL-1β	1.12 (0.04˜2.21)	0.52 (0.15˜0.89)	1.53 (-0.86˜3.92)	0.12 (0.04˜0.21)
IL-4	1.32 (-0.6˜3.25)	0.22 (0.04˜0.4)	0.43 (0.05–0.81)	0.21 (0.09˜0.32)
IL-6	13.43 (-5.05˜31.91)	21.79 (5.8˜37.8)	36.60 (-233.80˜97)	2.55 (0.48˜4.62)
IL-10	5.96 (-8.76˜20.67)	3.54 (-3.62˜10.7)	7.49 (-6.66˜21.65)	1.58 (-0.28˜3.22)
IL-12	10.5 (-15.62˜36.62)	7.1 (-4.7˜18.9)	15.29 (-18.848˜49.43)	0.43 (0.19˜0.66)
G−CSF	7.44 (2.30˜12.58)	13.32 (3.7˜22.9)	5.59 (0.83˜10.34)	1.18 (-0.017˜2.23)
IFN-γ	61.63 (-25.64˜148.89)	19.7 (-16.4˜55.8)	28.18 (-29.53˜85.88)	5.24 (0.66˜9.82)
MIP-1β	113.06 (-116.83˜342)	91.7 (52.8˜130.5)	111.73 (-0.41˜223.86)	48.99 (32.19˜65.80)
TNF-α	4.68 (-0.03˜9.38)	11.75 (-14.8˜38,3)	36.36 (-6.66˜79.39)	1.35 (0.11˜2.59)
PGE2*	329.5 (-43.8˜702.4)	170.5 (114.3˜226.8)	381.13 (54.66˜707.6)	Not tested

Febrile illness was observed within 24 h after immunization in 61 subjects: three bacterial vaccines with or without other vaccine (n = 30), two bacterial vaccines with or without other vaccine (n = 12), and single bacterial vaccine with or without other vaccine (n = 19). Eighteen serum samples were obtained from whom no febrile illness was observed within 24 h after immunization: three bacterial vaccines with or without other vaccine (n = 5), two bacterial vaccines with or without other vaccine (n = 7), and single bacterial vaccine with or without other vaccine (n = 6). Ten sera were obtained from normal healthy infants aged 4–15 mo of age. IL-1β, IL-4, IL-6, IL-10, IL-12, G-CSF, IFN-γ, MIP-1β, and TNF-α were assayed by Bio-Plex human 17-plex. PGE2* was assayed with the competitive EIA kit. Mean serum concentrations of cytokines are shown with 95% CI in parentheses.

Table 3. Comparison of cytokine profiles of acute phase sera obtained from admitted patients or outpatients with H1N1 pandemic 2009 influenza

Influenza	IL-1β	IL-6	G-CSF	TNF-α
Admitted	19.44	35.93	12.44	16.09
95% CI	0–54.29	19.19–52.66	7.47–17.41	3.67–28.50
Outpatients	0.8	19.5	6.26	6.55
95% CI	0–2.06	1.54–37.45	3.02–9.49	1.10–11.97