Clinical trial NCT02519361: Involvement of the Translation Initiation Factors in Resolution of Inflammation in the Elderly Population
Official title: The Involvement of the Translation Initiation Factors eIF4E and eIF4G in Resolution of Inflammation in the Elderly Population
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Infection in the Elderly
Keywords: elderly
immune response
acute infection
Lead sponsor: Meir Medical Center
Sponsor class: OTHER
First posted: 2015-08-10
Enrollment: 30
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: patients admitted to internal department due to acute infection

Brief summary: Aging cause specific changes in the immune system. Processes like "immunoessence" and "inflammaging" offend the functioning of the immune cells and expose the elderly patient to infections that can lead to morbidity and death.

Protein translation regulation offers a strategic advantage to the immune cells, because it enables rapid activation or termination of synthesis of specific proteins, required for inflammation or its resolution. Translation initiation depends on recruitment of eukaryotic initiation factor "eIF4F" complex.

The aim of the current study is to investigate the involvement of the translation initiation factors (eIF4E and eIF4G) in the process of recovery from acute infection in elderly patient admitted to the internal department with an acute infection.

Detailed description: 1. Blood samples of elderly patients diagnosed with acute infection (fever and leukocytosis) will be collected twice - at admittance to Meir hospital and after recovery (24-48 hours without fever and leukocytosis). evidence of infection (chest x ray, urine and blood samples) will be collected. participants will be divided to two age groups: 65-80 yrs and very old patient \>85 yrs, and will be compared to younger patients aged 50-65.
2. Peripheral blood samples will be separated to subpopulations of lymphocytes, monocytes and polymorphonuclears, and protein will be extracted.
3. protein lysates will be separated by SDS-PAGE electrophoresis and immunoblotted for phosphorylated and total eIF4E and eIF4G; their regulators: Mnk 1/2, 4EBP1, mTOR and targets: cyclin D1, c-Myc, survivin, BCL2, VEGFA, etc.
4. Paired samples (within each age group) will be analyzed and correlated with clinical response of the patients. The source of the infection will also be considered.
5. Comparison between age groups at admittance and upon recovery will be made (Unpaired).

Eligibility criteria: Inclusion Criteria:

* patient aged 50 y and more with:
* fever \>38c that started in the 48 hours prior to admission
* leukocytosis \>10.0 K/microLiter
* suspected source of infection by symptoms, lab results or imaging
* treatment with antibiotics started in the last 24 hours or is about to be started

Exclusion Criteria:

* patients who cannot sign the informed concent ( dementia)
* patients with active malignancy
* patients who are under chemotherapy

Primary outcomes:
measure: Translation initiation factors expression by immunoblotting, in leukocytes sub population
timeFrame: 1 week
Secondary outcomes:
measure: Translation initiation factors regulators expression by immunoblotting in leukocytes sub population
timeFrame: 1 week
measure: Translation initiation factors targets expression by immunoblotting in leukocytes sub population
timeFrame: 1 week
Other outcomes:
Locations:
Study officials:
affiliation: r.h.ayzenfeld
name: Rachel Heffez Ayzenfeld, MD
role: PRINCIPAL_INVESTIGATOR
References: