Table 2.

IL-18 and TNF-α as examples of factors with both pro- and anti-inflammatory activity identified in several large cohort studies.

Pro- and Anti-Inflammatory Factors		Evidence
IL-18	TNF-α	Population Characteristics	Data Processing	Reference
PCA1—Correlated with age, mortality, morbidity and age-related diseases		1010 participants (428 men, 582 women), aged 21–96 y	Cluster analysis	[75]
Positively correlated with age	Absence of correlation with age, mortality, and morbidity. Positively correlated with some age-related diseases	General population—InCHIANTI cohort	Individual associations
Significant independent predictor of 5- and 10-year mortality	Non-predictive of 5-year mortality	7043 participants (2995 men, 4048 women), aged 65–102 y	Fully adjusted correlation with 10-year mortality	[83]
		General population—includes CHS and InCHIANTI cohorts
No cluster reported	“Down”-regulation—Correlated with frailty outcomes	967 participants (416 men, 551 women), aged 65 y and older	Cluster analysis	[76]
Individually correlated with worsened mobility		General population—InCHIANTI cohort
NI	TNF-α related—Negatively correlated with knee strength, HPPB score, and grip strength; Positively correlated with 400-m walk time	1269 participants, aged 70–79 y	Cluster analysis	[77]
	Highest R2 of the TNF-α-related component for the HPPB score and knee strength	General non-frail population	Individual associations
NI	NI	285 participants (67 men, 218 women), aged 90 y and older with a 4-year follow-up	Correlation with 4-year mortality	[93]
		General population	Fully adjusted
Local inflammation-endothelial dysfunction	NI	320 participants (236 men, 84 women), aged 58–74 y with a 1-year follow-up	Cluster analysis	[78]
Independent predictor of 1-year recurrent coronary events		Acute coronary syndrome patients	Individual associations
Positively correlated with age	Absence of correlation with age	1327 participants (586 men, 741 women), aged 20–102 y	Correlation with age	[80]
Reduced the size of the regression coefficient for age	NR	General population—Includes InCHIANTI cohort	Adjustment for cardiovascular risk factors and morbidities
Proinflammation and anti-inflammation—Absence of association with 4-year death rate		580 women aged 31–85 y with a 4.7-year follow-up	Cluster analysis	[79]
		Clinically referred for coronary angiography
NI	Negatively correlated with walking and standing balance performance	1020 participants (483 men, 537 women), aged 65–102 y	Correlation with physical performance	[81]