Differential pattern of cytokine production by depressed medical students; evidence for involvement of cytokine network in pathology of depression.

BACKGROUND: Previous studies revealed that the immune responses of depressed patients can be affected by alteration of immune system factors; however, the immune genes mainly influenced are yet to be fully understood. Therefore, the main aim of present study was to identify serum levels of drastic inflammatory cytokines including IL-17A, IL-12, and IL-6 as well as anti-inflammatory cytokines, IL-10 and TGF-beta, amongst Iranian depressed medical students. METHODS: Peripheral blood specimens were collected from 38 Iranian medical student patients with moderate and severe depression along with 43 healthy students as control subjects. The serum levels of IL-17A, IL-12, IL-6, IL-10, and TGF-beta were assessed using the ELISA technique. RESULTS: Our results showed that the serum IL-10 level was significantly (p = 0.011) decreased in depressed patients (2.8 +/- 0.41 pg/mL) compared to healthy controls (4.3 +/- 0.4 pg/mL). The results also revealed that serum levels of TGF-beta were significantly increased in severely (12.75 +/- 5.22) compared to moderately (5.3 +/- 0.7) depressed patients (p = 0.045). CONCLUSIONS: According to the results of the present study, the decreased IL-10 level in the depressed patients may be responsible for the induction of inflammation in Iranian depressed patients. Additionally, increased serum levels of TGF-beta in severely compared to moderately depressed patients may be related to normal immune responses against inflammation in severely depressed patients.

The adapter proteins of TLRs, TRIF and MYD88, are upregulated in depressed individuals.

BACKGROUND AND AIMS: TRIF and MYD88 are intracellular adaptor proteins for TLR signaling, and altered expression of these molecules can lead to defective or unregulated immune responses. Furthermore, previous studies revealed that depression may alter immune responses, but its mechanisms of action are unclear yet. There is a possibility that immunity and depression are linked through molecules such as TRIF and MYD88, thus, the aim of this study was to evaluate the mRNA levels of TRIF and MYD88 in the PBMCs isolated from depressed medical students. MATERIAL AND METHODS: The current study examined 38 depressed medical students studying in Iran and 43 healthy students from the same cohort as a control group. The mRNA levels of TRIF and MYD88 were examined in parallel with a housekeeping gene using real-time PCR. RESULTS: Our results demonstrated that expression of TRIF and MYD88 were significantly elevated in PBMCs isolated from depressed patients when compared to healthy subjects. CONCLUSIONS: Based on the current results, it seems that chronic inflammation in depressed patients correlates to the over expression of TRIF and MYD88 genes. Our results show a possible link between the reported increases of chronic inflammation in depressed individuals with unbalanced expression of genes that regulate immunity.

Defective NF-kB transcription factor as the mediator of inflammatory responses: a study on depressed Iranian medical students.

BACKGROUND: NF-kB is a transcription factor that is a downstream target of several cell signaling systems including TLRs. Defective expression of the molecule can lead to inappropriate immune responses. Previous studies revealed that depression can affect immune responses, but its molecular mechanisms are yet to be fully understood. Thus, the main aim of this study was to identify if mRNA levels of NF-kB are changed in the PBMCs isolated from Iranian depressed medical students. METHODS: This cross-sectional study was done on 38 Iranian depressed medical students and 43 healthy students as a control group. The mRNA levels of NF-kB were assessed in parallel with beta-actin (as the housekeeping gene) using Real-Time PCR technique. RESULTS: Our results showed that mRNA levels of NF-kB were significantly decreased in isolated PBMCs from depressed patients compared to healthy controls. CONCLUSIONS: According to the results obtained in the present study, it seems that depressed patients are unable to appropriately express NF-kB at mRNA levels which may in turn lead to defective molecule expression.