Elevated Levels of Serum IL-5 are Associated With an Increased Likelihood of Major Depressive Disorder

Antti-Pekka Elomaa; Leo Niskanen; Karl-Heinz Herzig; Heimo Viinamäki; Jukka Hintikka; Heli Koivumaa-Honkanen; Kirsi Honkalampi; Minna Valkonen-Korhonen; Ilkka T Harvima; Soili M Lehto

Disclosures

BMC Psychiatry. 2012;12(2)

Abstract and Introduction

Abstract

Background Inflammatory mediators in both the peripheral circulation and central nervous system (CNS) are dysregulated in major depressive disorder (MDD). Nevertheless, relatively little is known about the role of the T-helper (Th)-2 effector cytokines interleukin (IL)-5 and IL-13 in MDD.
Methods We examined the serum levels of these cytokines and a Th-1 comparison cytokine, interferon (IFN)-γ, in 116 individuals (MDD, n = 58; controls, n = 58).
Results In our basic multivariate model controlling for the effects of potential confounders on the associations between MDD and the examined cytokines, each 1-unit increase in the serum IL-5 level increased the likelihood of belonging to the MDD group by 76% (OR 1.76, 95% CI 1.03–2.99, p = 0.04; model covariates: age, gender, marital status, daily smoking and alcohol use). The likelihood further increased in models additionally controlling for the effects of the use of antidepressants and NSAIDS, and a diagnosis of asthma. No such associations were detected with regard to IL-13 (OR 1.08, 95% CI 0.96–1.22, p = 0.22) or IFN-γ (OR 1.02, 95% CI 0.99–1.05, p = 0.23).
Conclusions Elevated levels of IL-5, which uses the neural plasticity-related RAS GTPase-extracellular signal-regulated kinase (Ras-ERK) pathway to mediate its actions in the central nervous system (CNS), could be one of the factors underlying the depression-related changes in CNS plasticity.

1 2 3 4 5 6

Next Section

Table 1. The characteristics of the study participants.
	MDD	Controls
	n = 58	n = 58	Statistics*	p-value
Age	53.40 ± 1.22	53.21 ± 1.20	t = −0.011	0.912^a
Female, n (%)	40 (69.0)	40 (69.0)	χ² = 0.00	1.000^b
Married or living with a partner, n (%)	48 (82.5)	55 (94.8)	χ² = 5.25	0.039^b
Daily smoking, n (%)	18 (31.0)	4 (6.9)	χ² = 10.99	0.001^b
Alcohol use, ≥ 2 times per week (%)	9 (15.5)	10 (17.2)	χ² = 0.06	0.802^b
Asthma, n (%)	3 (5.2)	5 (8.6)	χ² = 0.537	0.464^b
BMI (kg/m²)	27.24 ± 0.86	27.13 ± 0.65	Z = -0.04	0.967^c
HAM-D-21	12.00 ± 0.73	2.98 ± 0.36	Z = -8.00	< 0.001^c
ADS	2.84 ± 0.43	0.59 ± 0.13	Z = -4.04	< 0.001^c
HAM-D-29	14.84 ± 0.99	3.57 ± 0.41	Z = -7.86	< 0.001^c
BDI	17.68 ± 0.97	3.55 ± 0.41	Z = -8.77	< 0.001^c
Use of NSAIDs, n (%)	7 (12.1)	1 (1.7)	--	0.061^d
Use of oral corticosteroids, n (%)	5 (8.6)	3 (5.2)	--	0.717^d
Use of antidepressants, n (%)	22 (37.9)	4 (6.9)	χ² = 16.06	< 0.001^b
IL-5 (pg/ml)	0.81 ± 0.13	0.54 ± 0.08	Z = -1.87	0.061^c
IL-13 (pg/ml)	7.51 ± 6.05	0.89 ± 0.22	Z = -0.60	0.549^c
IFN-γ (pg/ml)	12.03 ± 5.96	3.03 ± 0.91	Z = -0.43	0.664^c
IFN-γ/IL-5 ratio	6.97 ± 1.99	24.69 ± 11.16	Z = -0.39	0.697^c

Values are means ± standard errors unless otherwise stated.
^a Student's t-test; ^b Chi-squared test; ^c Mann-Whitney U-test; ^d Fisher's exact test; * Where applicable
Abbreviations: ADS = atypical depression supplement; BMI = body mass index, BDI = Beck Depression Inventory, HAM-D = Hamilton Depression Rating Scale, IL = interleukin, MDD = major depressive disorder; NSAID = non-steroidal anti-inflammatory drug

Table 2. The likelihood for belonging to the major depressive disorder group.
		Age			Gender			Marital status			Daily smoking			Alcohol use			Cytokine*			Additional covariate (antidepressant/NSAIDs/asthma)
	Model	OR	P	CI95_%	OR	p	CI95_%	OR	p	CI95_%	OR	p	CI95_%	OR	p	CI95_%	OR	p	CI95_%	OR	p	CI95_%
IL-5*	1.^a	1.03	0.24	0.98–1.08	1.37	0.49	0.56–3.35	4.05	0.67	0.91–17.96	7.95	0.001	2.34–27.03	1.62	0.40	0.52–5.04	1.76	0.04	1.03–2.99	-	-	-
	2.^b	1.01	0.69	0.96–1.06	1.51	0.41	0.56–4.06	4.23	0.85	0.82–21.76	10.59	0.001	2.87–39.15	2.32	0.18	0.68–7.88	2.06	0.013	1.16–3.64	11.98	0.001	3.25–44.16
	3.^c	1.04	0.15	0.99–1.09	1.30	0.58	0.52–3.30	3.99	0.076	0.87–18.39	9.08	0.001	2.60–31.73	1.94	0.29	0.57–6.53	1.89	0.022	1.10–3.27	0.084	0.033	0.01–0.82
	4.^d	1.03	0.24	0.98–1.08	1.31	0.56	0.53–3.25	3.80	0.81	0.85–17.01	8.60	0.001	2.46–30.09	1.67	0.38	0.54–5.17	1.83	0.028	1.07–3.14	2.45	0.30	0.45–13.43
IL-13*	1^.a	1.03	0.23	0.98–1.08	1.26	0.61	0.52–3.03	4.50	0.044	1.04–19.50	7.51	0.001	2.22–25.33	1.47	0.50	0.48–4.50	1.08	0.22	0.96–1.22	-	-	-
	2.^b	1.01	0.69	0.96–1.06	1.30	0.59	0.50–3.36	4.49	0.066	0.91–22.24	9.24	0.001	2.54–33.58	2.02	0.26	0.60–6.84	1.06	0.33	0.94–1.20	0.098	0.001	0.027–0.35
	3.^c	1.04	0.15	0.99–1.09	1.19	0.71	0.48–2.94	4.35	0.054	0.97–19.47	8.36	0.001	2.41–29.07	1.70	0.39	0.51–5.63	1.09	0.186	0.96–1.24	0.095	0.039	0.10–0.89
	4.^d	1.03	0.22	0.98–1.08	1.20	0.69	0.49–2.91	4.24	0.055	0.97–18.54	8.18	0.001	2.35–28.52	1.47	0.50	0.48–4.50	1.10	0.14	0.97–1.24	2.65	0.29	0.44–15.87
IFN-γ*	1.^a	1.03	0.21	0.98–1.08	1.32	0.54	0.55–3.19	3.92	0.069	0.90–17.09	7.41	0.001	2.19–25.14	1.61	0.42	0.51–5.05	1.02	0.23	0.99–1.05	-	-	-
	2.^b	1.01	0.66	0.96–1.06	1.31	0.57	0.51–3.40	3.86	0.094	0.80–18.74	8.95	0.001	2.46–32.47	2.15	0.23	0.62–7.41	1.01	0.22	0.99–1.04	0.10	0.001	0.029–0.37
	3.^c	1.04	0.15	0.99–1.09	1.22	0.67	0.49–3.02	4.18	0.062	0.93–18.85	8.04	0.001	2.32–27.83	1.74	0.37	0.52–5.80	1.02	0.25	0.99–1.05	0.11	0.053	0.011–1.03
	4.^d	1.03	0.21	0.98–1.08	1.28	0.59	0.53–3.11	3.77	0.078	0.86–16.49	7.63	0.001	2.23–26.16	1.61	0.41	0.52–5.05	1.02	0.23	0.99–1.05	1.72	0.52	0.33–8.88

^a Covariates for Model 1: gender, age, marital status, daily smoking, and alcohol use
^b Covariates for Model 2: gender, age, marital status, daily smoking, alcohol use, and antidepressant use
^c Covariates for Model 3: gender, age, marital status, daily smoking, alcohol use, and NSAIDs use
^d Covariates for Model 4: gender, age, marital status, daily smoking, alcohol use, and diagnosis of asthma

Comments

Commenting is limited to medical professionals. To comment please Log-in.

Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.